1. Respiratory System Lecture 2 Gas Exchange & Regulation

2. Gas Exchange occurs between blood & alveolar air across respiratory membrane by diffusion due to concentration gradient –differences between O 2 & CO 2 concentrations –measured by partial pressures greater difference in partial pressures  greater rate of diffusion need to understand partial pressures & diffusion of gases into & out of liquids to understand gas exchange

3. Dalton’s Law of Partial Pressure air-mixture of gases & water vapor consists of N 2 -78%-most abundant, O 2 -20.9%water, CO 2, Argon atmospheric pressure is result of collision of all gas molecules at any time 78.6% of collisions involve N 2 & 20.9% involve O 2 each gas contributes to total pressure in proportion to its relative abundance-Dalton’s Law PressureTotal = Pressure1 + Pressure2... Pressuren pressure contributed by one gas is partial pressure directly proportional to % of gas in mixture all partial pressures added = total pressure exerted by gas mixture =760mm Hg PN 2 -parital pressure nitrogen = 78.6 X 760 mm Hg-597 mm Hg PO 2 20.9 X 760 = 159 mm Hg

4. Henry’s Law at a given temperature, amount of gas in solution is directly proportional to partial pressure (pp) of gas when gas mixture is in contact with liquid, each gas dissolves in proportion to its partial pressure actual amount in solution at given pp depends on solubility of that gas in that liquid

5. Partial Pressures in Alveoli & Alveolar Capillaries oxygen diffuses from alveolar air (PP is 105mm Hg) into blood in pulmonary capillaries where P O2 is 40 mm Hg when O 2 is diffusing from alveolar air into deoxygenated blood CO 2 is diffusing in opposite direction PCO 2 of deoxygenated blood is 45 mm Hg PCO 2 of alveolar air-40 mm Hg CO 2 diffuses from deoxygenated blood into alveoli left ventricle pumps oxygenated blood into aorta & through systemic arteries to systemic capillaries exchange of O 2 & CO 2 between systemic capillaries & tissues cells P O2 of blood in systemic capillaries is 100 mmHg in tissue cells it is 40mm Hg as oxygen diffuses out of capillaries into tissues carbon dioxide diffuses in opposite direction PCO 2 of cells is 45 mm Hg it is 40mm Hg systemic capillary blood

6. Diffusion at Respiratory Membrane efficient large PP differences across membrane –larger PP  faster diffusion capillary & alveolar membranes are fused  distances for diffusion- small gases are soluble in lipid- pass through surfactant layer easily surface area is huge

7. Gas Transport Major function of blood O 2 Co 2

8. Oxygen Transport dissolved in plasma –normal PO 2 of alveoli, 100ml of blood contains 0.3ml of O 2 carried in RBC bound to hemoglobin

9. Hemoglobin 4 subunits –2  & 2ß globular protein chains each has one heme group each heme has one iron each Fe can bind one O 2 every Hb can carry 4 O 2 s there are 280 X 10 6 Hb molecules/RBC each RBC could carry billion O 2 molecules

10. Oxyhemoglobin Hb + O 2  HbO 2 - oxyhemoglobin reversible Fe-O 2 bond-weak easily broken without altering either Hb or O 2 HbO 2  O 2 + Hb deoxyhemoglobin

11. Amount of Oxygen Bound to HB PO 2 of plasma most important factor determining how much O 2 binds to Hb actual amount bound/maximum that could bind = % saturation all binding sites occupied-100% saturation

12. Oxyhemoglobin Dissociation Curve plots % saturation Hb (number of O 2 bound) against PO 2 –relates saturation of Hb to PP of O 2

13. HbO 2 Dissociation Curve not linear-S-shaped steep slope-flattens or plateaus shape due to subunits of Hb each time Hb binds one O 2  shape changes slightly  increases ability of Hb to bind another O 2 when P O2 is between 60 - 100mmHG, Hb is 90% or more saturated with oxygen blood picks up nearly full load of O 2 from lungs even when P O2 alveolar air is as low as 60mmg Hg increasing PO 2 above 80mm Hg adds little to O 2 content of blood PO 2 < 50 mm, small drops in PO 2 cause large release of O 2

14. Importance of Oxyhemoglobin Dissociation Curve shape of Hb saturation curve extremely important over steep initial slope  very small decreases in PO 2  results in very large changes in amount of O 2 bound or released from Hb ensures near normal O 2 transport even when O 2 content of alveolar air decreases (important at high altitudes) slope of curve allows blood to have high O 2 content at fairly low PO 2 s PO 2 can fall considerably-without greatly reducing oxygen supply

15. Factors Affecting Affinity of O 2 & Hb various factors increase or decrease affinity (tightness of bond) of Hb to O 2 factors will shift curve to left (higher affinity) or to right (lower affinity) left-more O 2 is bound than released right-more O 2 is released than bound pH p CO2 temperature BPG

16. Hb & pH as pH decreases  shape of Hb changes  releases O 2 more readily  slope of curve changes  saturation decreases more O 2 released curve shifts to right effect of pH on Hb saturation is Bohr Effect

17. Bohr Effect Hb acts as buffer for H + when H + bind to amino acids in Hb they alter its structure slightly decreasing its oxygen carrying capacity increased H + ion concentration causes O 2 to unload from Hb binding of O 2 to Hb causes unloading of H + from Hb elevated pH (lowered H + ) increases affinity of Hb for O 2 shifts O 2 -Hb dissociation curve to left

18. Hb & Temperature higher temperature –curve shifts to right –unloading of O 2 from Hb is increased lower temperatures –curve shifts to left –O 2 binds more to Hb

19. Hb & Carbon Dioxide increase in CO 2 –s–shifts curve to right more O 2 released decrease in CO 2 –s–shifts curve to left more O 2 bound

20. Hb & BPG BPG-2,3 biphosphoglycerate –produced by RBC during glycolysis higher levels –unloading of oxygen increased –shifts to right BPG decreases –curve shifts to left –more oxygen is bound amount of BPG generated drops as RBCs age BPG drops too low  O 2 irreversibly bound to Hb

21. CO 2 Transport dissolved in plasma –7% transported as HCO 3 (bicarbonate ion) –70% bound to HB –23% –attaches to –NH 2 groups (amino) of histidine –Carbaminohemoglobin HB-CO 2

22. Transport as HCO 3 converted to carbonic acid –unstable –dissociates to hydrogen & bicarbonate ions HCO 3 - diffuses from RBCs into plasma exchanges one HCO 3 - for one Cl- –chloride shift –maintains electrical neutrality

23. AT LUNG

24. AT TISSUES

25. Control of Respiration normally cellular rates of absorption & generation of gases are matched by capillary rates of delivery & removal rates are identical to rates of O 2 absorption & CO 2 excretion at lungs if absorption & excretion become unbalanced –homeostatic mechanisms restore equilibrium changing blood flow & O 2 delivery –locally regulated changing depth & rate of respiration –respiratory centers in brain

26. Respiratory Centers in Brain usually breath without conscious thought- involuntary –depends on repetitive stimuli from brain automatic, unconscious cycle of breathing controlled by respiratory centers in medulla & pons medullary rhymicity area pneumotaxic center apneustic center

27. Medullary Rhymicity Center controls basic rhythm of respiration has an inspiratory & expiratory area nerves project to diaphragm by phrenic nerve & to intercostals by intercostal nerves quiet breathing neuron activity increases for 2 sec.  stimulates inspiratory muscles rib cage expands as diaphragm contracts –inhalation occurs output ceases abruptly  muscles relax  elastic parts recoil  exhalation (lasts 3 seconds) neurons begins to fire again cycle repeats

28. Pneumotaxic & Apneustic Centers located in pons –regulates shift from inspiration to expiration regulate respiratory rate & depth of respiration in response to sensory stimuli or input from other brain centers pneumotaxic center-upper pons transmits inhibitory impulses to inspiratory area helps turn off inspiratory area before lungs become too full of air increased pneumotaxic output  quickens respiration by shortening duration of each inhalation  breathing rate increases decreased output  slows respiratory pace depth of respiration increases apneustic center sends stimulating impulses to inspiratory area activates it producing prolonged inhalation. result is long, deep inhalations

29. Regulation of Respiratory Centers conscious or voluntary control inhale or exhale at will input form cerebral motor cortex stimulates motor neurons to stimulate respiratory muscles bypassing medulla centers limited-impossible to override chemoreceptor reflexes nerve impulses from hypothalamus & limbic system also stimulate respiratory center allows emotional stimuli to alter respiration

30. Respiratory Reflexes brain centers regulate respiratory rate & depth of respiration –in response to sensory stimuli or input from other brain centers sensory information comes from central chemoreceptors peripheral chemoreceptors proprioceptors stretch receptors information from these alters patterns of respiration changes are respiratory reflexes

32. Chemoreceptors central chemoreceptors neurons in brainstem that respond to changes in pH of cerebrospinal fluid stimulation increases depth & rate of respiration peripheral chemoreceptors –carotid & aortic bodies of large arteries –respond to PCO 2, pH & PO 2 of blood

33. Respiratory Reflex-CO 2 Hypercapnia –increase in PCO 2 CO 2 crosses blood brain barrier rapidly rise in arterial PCO 2 almost immediately elevates CO 2 levels in CSF  pH decreases  excites central chemoreceptors  stimulates respiratory centers  increases depth & rate of breathing rapid breathing moves more air in & out of lungs  alveolar CO 2 decreases  accelerates diffusion of CO 2 out of alveolar capillaries  homeostasis restored results in hyperventilation

34. Chemoreceptor Reflexes-CO 2 hyperventilation  hypocapnia –low PCO 2 central & peripheral chemoreceptors are not stimulated Inspiratory center sets its own pace CO2 accumulates homeostasis restored

36. Stretch Receptors found in smooth muscles of bronchi & bronchioles & in visceral pleura lung inflation signal inspiratory & apneustic areas via vagus nerve Inhibits both Hering-Breuer Reflex