1. RESPIRATION Dr. Zainab H.H Dept. of Physiology Lec9,1o

2. objectives Determine the factors that affect OHDC Discriminate between Bohr & Haldane effect on O2 &CO2 transport Describe the effect of respiration on acid – base balance of the blood

3. OHDC and Exercise  During mild exercise:  venous PO 2 decrease from 40 mmHg to 30 mmHg  change in percent saturation from 75% to 58%.  arterial percent saturation still 97%.  The lowered venous percent saturation indicates that more O 2 has been unloaded to the tissues.

4. OHDC and Exercise  In the preceding example:  97% – 75% = 22% unloading at rest  97% – 58% = 39% unloading during mild exercise.  During heavier exercise, the venous PO 2 can drop to 20 mmHg or lower, indicating a percent unloading of about 80%.  This occurs as a result of the lowered pH and increased temperature in exercising muscles.

5. Bohr Effect The affinity of Hb for O 2  in response to  blood CO 2 and a  in pH.  pH can be  by CO 2 (through the formation of H 2 CO 3 )  If the affinity is  : there is slightly less loading of the blood with O 2 in the lungs but greater unloading of O 2 in the tissues.  The net effect is that the tissues receive more O 2 when the blood pH is lowered.  Bohr effect provide more O 2 to the tissues (when their CO 2 output is  ) during physical exercise by a faster metabolism

6. Bohr Effect  When OHDC is graphed at different pH values:  shifted to the right by  pH and shifted to the left by  pH.  If the percent unloading is calculated, it will be seen that a shift to the right of the curve indicates a greater unloading of O 2.  A shift to the left, indicates less unloading but slightly more O 2 loading in the lungs.

9. Effect of temperature on OHDC  When OHDC is constructed at different temperatures:   temperature  curve moves rightward  indicates that  affinity of HB for O 2.  An  in temperature weakens the bond between Hb and O 2 and thus has the same effect as a fall in pH.  At higher temperatures, therefore, more O 2 is unloaded to the tissues.  This effect enhance the delivery of O 2 to muscles that are warmed during exercise.

11. Effect of 2,3-DPG on O 2 Transport  RBCs lacks mitochondria, so energy obtained through the anaerobic metabolism of glucose.  One metabolite of this reaction is 2,3-diphosphoglyceric acid (2,3-DPG).  The enzyme that produces 2,3-DPG is inhibited by oxyHb.  2,3-DPG production is increased by  in oxyHb.   2,3-DPG production occur in: i. Low total Hb concentration (in anemia) ii. PO 2 is low (at a high altitude, for example).

12. Effect of 2,3-DPG on O 2 Transport  Bonding of 2,3-DPG with deoxyHb makes the latter more stable.  Therefore, a higher proportion of the oxyHb will be converted to deoxyHb by the unloading of its O 2.   concentration of 2,3-DPG in RBCs  increases O 2 unloading and shifts the OHDC to the right.

14. Fetal Hemoglobin  Has 2  -chains in place of the  -chains.  Normal HbA in the mother is able to bind to 2,3-DPG in contrast to HbF, and thus has a higher affinity for O 2 than does HbA.  Since HbF can have a higher percent oxyHb than HbA at a given PO 2, O 2 is transferred from the maternal to the fetal blood through the placenta regardless of the PO 2 in the maternal blood.  The dissociation curve of HbF is shifted to the left.

15. Anemia  Total Hb concentration  below normal  each RBC produces more 2,3-DPG.  Normal Hb concentration of 15g/100 ml unloads about 4.5 ml O 2 /100 ml at rest.  If the Hb concentration were  by half?  Under these conditions, as great as 3.3 ml O 2 /100 ml is unloaded to the tissues.  Because: rise in 2,3-DPG production causes  in the affinity of Hb for O 2.

16. If the hemoglobin–O2 dissociation curves shift to the right this could be caused by (A) increased pH (B) decreased 2,3-diphosphoglycerate (DPG) concentration (C) strenuous exercise (D) fetal hemoglobin (HbF) (E) carbon monoxide (CO) poisoning

17. Muscle Myoglobin  Red pigment found in:  slow-twitch, aerobically respiring skeletal fibers  cardiac muscle cells.  Differ from Hb, it has one heme  combine with only one O 2 molecule.  Has a higher affinity for O 2 than Hb.  Its dissociation curve is shifted to the left of OHDC.  The shape of the curve is different from the OHDC (rectangular), indicating that O 2 will be released only when the PO 2 becomes very low.

18. Muscle Myoglobin  Myoglobin may also have an O 2 -storage function, which is of particular importance in the heart.  During diastole, when the coronary blood flow is greatest, myoglobin can load up with O 2. This stored O 2 can then be released during systole, when the coronary arteries are squeezed closed by the contracting myocardium.

20. CO 2 Transport  CO 2 is carried by the blood in three forms: A. Dissolved CO 2 (10%): 21 times more soluble than O 2 in water.  H 2 O + CO 2  H 2 CO 3 B. Carbaminohemoglobin (20%)  CO 2 + Hb  HbCO 2 C. HCO 3 - (70%).  In the RBCs through the action of Carbonic anhydrase. )  CO 2 + H 2 O  H 2 CO 3  [H + ] + [HCO 3 - ]

21. CO 2 Transport   CO 2 combine with H 2 O to form H 2 CO 3.  This occurs spontaneously in the plasma at a slow rate  Within the RBCs it occurs much more rapidly because of the catalytic action of the enzyme carbonic anhydrase.  Since this enzyme is confined to the RBCs, most of the H 2 CO 3 is produced there rather than in the plasma. CO 2 + H 2 O H 2 CO 3 high PCO 2

22. Haldane Effect  Removal of O 2 from Hb increases its affinity for CO 2.  This allows CO 2 to “ride” on the empty Hb.  Is opposite to the Bohr effect.  Is quantitatively more important than the Bohr effect.  It promotes the transfer of CO 2

23. Cl - Shift at Systemic Capillaries  The buildup of H 2 CO 3 concentrations within the RBCs favors the dissociation of these molecules into H + and HCO 3 -  H 2 CO 3  H + + HCO 3 -  The H + released by the dissociation of H 2 CO 3 are largely buffered by their combination with deoxyHb within the RBCs.

24. Cl - Shift at Systemic Capillaries  Most of the HCO 3 - formed (unlike H + ) in the RBC, diffuses out into the plasma.  As a result: trapping of H + within RBCs and the outward diffusion of HCO 3 -  inside of the RBC gains a net positive charge.  This attracts Cl - to move into the red blood cells as HCO 3 - moves out.  This is known as the chloride shift.

25. Hamburger Effect  All of the HCO 3 - and Cl - generated following CO 2 carriage by the RBC increases the intracellular osmotic pressure.  This causes the cell to swell with extra H 2 O that diffuses through the cell membrane.  This is called “Hamburger effect.”  This is why the haematocrit (HCT) of venous blood is 3% higher than in arterial blood.

26. In the transport of CO2 from the tissues to the lungs, which of the following occurs in venous blood (A) Conversion of CO2 and H2O to H+ and HCO3 –in the red blood cells (RBCs) (B) Buffering of H+ by oxyhemoglobin (C) Shifting of HCO3– into the RBCs from plasma in exchange for Cl– (D) Binding of HCO3 – to hemoglobin (E) Alkalinization of the RBCs

27. Reverse Cl - Shift at Pulmonary Capillaries  When blood reaches the pulmonary capillaries, deoxyHb is converted to oxyHb.  oxyHb has weaker affinity for H + than deoxyHb  H + are released within the RBCs.  This attracts HCO 3 - from the plasma, which combines with H + to form H 2 CO 3 in the RBC  RBC becomes more negative & Cl - diffuses out (reverse Cl - shift).  H + + HCO 3 -  H 2 CO 3 CO 2 + H 2 O H 2 CO 3 Low PCO 2

29. Effects of CO  CO is toxic because it reacts with Hb to form COHb, and COHb cannot take up O 2.  The affinity of Hb for CO is 210 times its affinity for O 2, and COHb liberates CO very slowly.  In the presence of COHb, the dissociation curve of the remaining HbO 2 shifts to the left, decreasing the amount of O 2 released.  The amount of COHb formed depends on the duration of exposure to CO as well as the concentration of CO in the inspired air and the alveolar ventilation.

30. Effects of CO  there is little stimulation of respiration because: A. arterial blood PO 2 remains normal B. carotid and aortic chemoreceptors are not stimulated.  The cherry-red color of COHb is visible in the skin, nail beds, and mucous membranes.  Death results when about 70–80% of the circulating Hb is converted to COHb.

31. Hypercapnia  CO 2 retention in the body.  initially stimulates respiration, alveolar ventilation increases and the extra CO 2 is expired, but it accumulates when ventilation is compromised.  Retention of larger amounts produces confusion, diminished sensory acuity, and, eventually, coma with respiratory depression and death.  In patients with these symptoms, the PCO 2 is markedly elevated, severe respiratory acidosis is present, and the plasma HCO 3 – may exceed 40 mEq/L.

32. Hypercapnia  Hypercapnia is exacerbated in ventilation– perfusion inequality and when alveolar ventilation is inadequate when CO 2 production is increased.  In febrile patients there is a 13% increase in CO 2 production for each 1°C rise in temperature  High carbohydrate intake increases CO 2 production because of the increase in the respiratory quotient.

33. Hypocapnia  Resulted from hyperventilation.  In voluntary hyperventilation, the arterial PCO 2 falls from 40  15 mm Hg while the alveolar PO 2  120 to 140 mm Hg.  Neurotic patients (chronically hyperventilate) show effects of hypocapnia.  Reduced cerebral blood flow by 30% or more (direct constrictor effect of hypocapnia on the cerebral vessels).  The cerebral ischemia causes light-headedness, Dizziness, Paresthesias.

34. Hypocapnia  Hypocapnic patients show signs of respiratory alkalosis: blood pH increased to 7.5 or 7.6.  The plasma HCO 3 – level is low, but HCO 3 – reabsorption is decreased because of the inhibition of renal acid secretion by the low PCO 2.

35. Respiratory Acid-Base Balance  Ventilation normally adjusted to keep pace with metabolic rate.  H 2 CO 3 produced converted to CO 2, and excreted by the lungs.  H 2 O + CO 2  H 2 CO 3  H + + HCO 3 -

36. Respiratory Acidosis  Hypoventilation.  Accumulation of CO 2 in the tissues.  P CO 2 increases.  pH decreases.  Plasma HCO 3 - increases.

37. Respiratory Alkalosis  Hyperventilation.  Excessive loss of CO 2.  P CO 2 decreases.  pH increases.  Plasma HCO 3 - decreases.

38. In acid base balance the normal plasma PCO2 and bicarbonate levels are disturbed. Match the changes in these parameters given below with the disorders in the drop down list Low plasma PCO 2 High plasma PCO 2 Decreased plasma bicarbonate (HCO 3 - ) Increased plasma bicarbonate HCO 3 -