1. OXYHEMOGLOBIN DISSOCIATION CURVE Dr. S. Parthasarathy MD., DA., DNB(anaes), MD (Acu), MD., DA., DNB(anaes), MD (Acu), Dip. Diab. DCA, Dip. Software statistics PhD (physio) Mahatma Gandhi medical college and research institute, puducherry – India

2. HOPE THIS WOULD BE A VERY HOPE THIS WOULD BE A VERY USEFUL LECTURE USEFUL LECTURE OR ATLEAST IT WILL BE A ------- --FUL LECTURE OR ATLEAST IT WILL BE A ------- --FUL LECTURE

3. ANAESTHETISTS DO PREANAESTHETIC CHECK UP ANAESTHETISTS DO PREANAESTHETIC CHECK UP What is important ??

5. LAVOISIER AND LAPLACE 1779 INTAKE OF SOME GASES WAS RESPIRATION AND IT PRODUCED SOME ACID INTAKE OF SOME GASES WAS RESPIRATION AND IT PRODUCED SOME ACID OXY= ACID OXY= ACID GENE= PRODUCER. GENE= PRODUCER.

6. ATMOSPHERIC AIR NITROGEN = 78% NITROGEN = 78% OXYGEN = 21% OXYGEN = 21% ARGON = 0.9% ARGON = 0.9% CO 2 = 0.03% CO 2 = 0.03% TRACES OF HELIUM,NEON AND KRYPTON TRACES OF HELIUM,NEON AND KRYPTON

7. BAROMETRIC PRESSURE P B = 760 mm Hg 760 × 21/100 =160 mm Hg. 760 × 21/100 =160 mm Hg. (P B × Fio2) (P B × Fio2) HUMIDIFIED IN THE AIRWAYS. P H2O = 47 mmHg. PIO2 = (760-47) × 21/100 = 150 mmHg. 150 mmHg.

8. ALVEOLUS -- CO2 DILUTES PA0 2 = PIO 2 – PACO 2 / RQ = 150 - 45 = 105 = 150 - 45 = 105 RQ = RESPIRATORY QUOTIENT CO 2 PRODUCED / O 2 CONSUMED

10. ALVEOLUS ALVEOLUS ↓ O 2 ↓ O 2 PLASMA PLASMA ↓ O 2 ↓ O 2 DISSOLVED OXYGEN DISSOLVED OXYGEN ↓ TRANSFERRED TO Hb TRANSFERRED TO Hb Pa O 2 100 mm Hg

11. 160 -150-105-100- 40-25-4 160 -150-105-100- 40-25-4 oxygen cascade oxygen cascade

13. OXYGEN CARRIAGE IN TWO FORMS DISSOLVED — 0.3 ml / 100ml DISSOLVED — 0.3 ml / 100ml Very less but., Very less but., IT IS IMPORTANT IT IS IMPORTANT –IT DETERMINES PaO2 –IT TRANSFERS O2 TO HAEMOGLOBIN. –IT IS THIS SMALL QUANTITY WHICH DIFFUSES TO TISSUES FIRST.

14. HEMOGLOBIN 1 gm of Hb carries 1.34 ml-1.39 ml of O 2 1 gm of Hb carries 1.34 ml-1.39 ml of O 2 19.5-19.7 ml oxygen / 100 ml 19.5-19.7 ml oxygen / 100 ml Dissolved + Hb oxygen= 20 ml Dissolved + Hb oxygen= 20 ml 200 ml / litre or 1000 ml / 5 litre 200 ml / litre or 1000 ml / 5 litre

15. 1000 ml o 2 supplied 250 ml consumed 250 ml consumed 750 ml returned 750 ml returned SvO2 75% SvO2 75% Oxygen flux = CARDIAC OUTPUT × 1.34 × Hb × SATURATION Oxygen flux = CARDIAC OUTPUT × 1.34 × Hb × SATURATION

16. HEMOGLOBIN= HEME+GLOBIN FOUR HEME MOLECULES +GLOBIN (FOUR CHAINS ) FOUR HEME MOLECULES +GLOBIN (FOUR CHAINS ) 2 ALPHA AND 2 BETA CHAINS. 2 ALPHA AND 2 BETA CHAINS. FOUR HEMES (FERROPROTOPORPHYRIN ) CAN ATTACH 4 OXYGEN MOLECULES FOUR HEMES (FERROPROTOPORPHYRIN ) CAN ATTACH 4 OXYGEN MOLECULES O2 + FERROUS = FERRIC → SATURATION → OXYGENATED Hb O2 + FERROUS = FERRIC → SATURATION → OXYGENATED Hb

19. COOPERATIVE EFFECT. OXYGEN ENTRY TO Hb PROMOTES FURTHER ENTRY BY INCREASING THE AFFINITY UPTO 500 TIMES TO SUCK MORE O2----POSITIVE COOPERATIVE EFFECT. OXYGEN ENTRY TO Hb PROMOTES FURTHER ENTRY BY INCREASING THE AFFINITY UPTO 500 TIMES TO SUCK MORE O2----POSITIVE COOPERATIVE EFFECT. IN DOWNLOADING IN TISSUES. REVERSE IS NEGATIVE COOPERATIVE EFFECT IN DOWNLOADING IN TISSUES. REVERSE IS NEGATIVE COOPERATIVE EFFECT

20. Parrots and parents Hemoglobin and oxygen act a little like parents and children. When all are living at home (i.e. hemoglobin is fully saturated) then the parents don’t want any to leave: Hemoglobin and oxygen act a little like parents and children. When all are living at home (i.e. hemoglobin is fully saturated) then the parents don’t want any to leave: but once one has flown the nest (i.e. dissociated from hemoglobin) – parents find it progressively easier to let go. but once one has flown the nest (i.e. dissociated from hemoglobin) – parents find it progressively easier to let go.

21. What this means that the conformation of the hemoglobin molecule depends on the number of molecules bound: What this means that the conformation of the hemoglobin molecule depends on the number of molecules bound: as one molecule of oxygen becomes unbound, the affinity for the others falls [and vice-versa]. as one molecule of oxygen becomes unbound, the affinity for the others falls [and vice-versa]. This is represented by the oxyhemoglobin dissociation curve. This is represented by the oxyhemoglobin dissociation curve.

22. Why the curve is sigmoid ?? COOPERATIVE EFFECT CAUSES THE CURVE TO BE SIGMOID. COOPERATIVE EFFECT CAUSES THE CURVE TO BE SIGMOID. R FORM (RELAXED) –OXYGENATED R FORM (RELAXED) –OXYGENATED T FORM (TAUT) - DE OXYGENATED T FORM (TAUT) - DE OXYGENATED

24. BEFORE THE CURVE – A BREAK A LADY PATIENT ENTERED A DOCTOR’S (MALE) CABIN AND SAID A LADY PATIENT ENTERED A DOCTOR’S (MALE) CABIN AND SAID “ SIR, CAN I ASK MY HUSBAND ALSO TO COME INSIDE.” “ SIR, CAN I ASK MY HUSBAND ALSO TO COME INSIDE.” DOCTOR : “ BELIEVE ME, I AM A GENTLEMAN.” DOCTOR : “ BELIEVE ME, I AM A GENTLEMAN.”

25. LADY PATIENT : LADY PATIENT : “SIR I BELIEVE YOU., BUT I DON’T BELIEVE MY HUSBAND AND YOUR NURSE OUTSIDE” “SIR I BELIEVE YOU., BUT I DON’T BELIEVE MY HUSBAND AND YOUR NURSE OUTSIDE”

27. CURVE OF PaO2 TO SaO2 PaO2 SaO2 27 50 (P 50 ) 40 75 (VENOUS) 60 90 100 98

29. P 50 = 27, Rt and left

30. SHIFT TO RIGHT = P 50 > 27 SHIFT TO RIGHT = P 50 > 27 SHIFT TO LEFT= P 50 < 27 SHIFT TO LEFT= P 50 < 27 RIGHT SHIFT AT ANY PaO2 LESS AFFINITY,LESS SATURATION RIGHT SHIFT AT ANY PaO2 LESS AFFINITY,LESS SATURATION INCREASED H + IONS (ACID) INCREASED H + IONS (ACID) INCREASED PCO2, INCREASED PCO2, INCREASED TEMP INCREASED TEMP INCREASED 2-3 DPG INCREASED 2-3 DPG

33. BOHR EFFECT ↑ PCO2 AND ACIDOSIS CAUSE RT. SHIFT ↑ PCO2 AND ACIDOSIS CAUSE RT. SHIFT H + IONS BIND TO GLOBIN CHAINS TO EFFECT A CONFORMATIONAL CHANGE IN HEME ATTACHMENT FAVOURING UNLOADING OF O 2 ( WE WANT TO HAPPEN IN TISSUES.) H + IONS BIND TO GLOBIN CHAINS TO EFFECT A CONFORMATIONAL CHANGE IN HEME ATTACHMENT FAVOURING UNLOADING OF O 2 ( WE WANT TO HAPPEN IN TISSUES.)

34. HALDANE EFFECT DEOXYGENATED BLOOD CAN PICK UP MORE CO 2 DEOXYGENATED BLOOD CAN PICK UP MORE CO 2 THINK OF TISSUES : THINK OF TISSUES : UNLOADING O2 → DEOXYGENATED BLOOD → PICKS UP MORE CO2 UNLOADING O2 → DEOXYGENATED BLOOD → PICKS UP MORE CO2

35. 15 DAYS OLD BLOOD CAN CAUSE DECREASED 2-3 DPG LEVELS TO SHIFT LEFT--LESS UNLOADING AND MORE AFFINITY (KENNEDY EFFECT) 15 DAYS OLD BLOOD CAN CAUSE DECREASED 2-3 DPG LEVELS TO SHIFT LEFT--LESS UNLOADING AND MORE AFFINITY (KENNEDY EFFECT) 24-48 HOURS TO BECOME NORMAL. 24-48 HOURS TO BECOME NORMAL.

36. What is the role of 2-3 DPG ?? In the deoxygenated T conformer, a cavity capable of binding 2,3-BPG forms in the center of the molecule. 2,3-BPG can occupy this cavity stabilizing the T state. Conversely, when 2,3-BPG is not available, or not bound in the central cavity, Hb can be converted to HbO2 more readily. In the deoxygenated T conformer, a cavity capable of binding 2,3-BPG forms in the center of the molecule. 2,3-BPG can occupy this cavity stabilizing the T state. Conversely, when 2,3-BPG is not available, or not bound in the central cavity, Hb can be converted to HbO2 more readily.

37. Useful increase in 2-3 BPG HIGH ALTITUDE. HIGH ALTITUDE. COPD COPD CYANOTIC HEART DISEASE CYANOTIC HEART DISEASE SEVERE ANEMIAS. SEVERE ANEMIAS.

38. FETAL Hb

40. Fetal Hb (higher affinity) Umbilical venous blood (20-25 mmHg O2) Umbilical venous blood (20-25 mmHg O2) DOUBLE BOHR EFFECT DOUBLE BOHR EFFECT Transfer of acids from fetal blood to maternal intervillous spaces— maternal Hb more acidic Rt shift—more unloading to fetus…fetal alkalosis shift to left-Hb F more affinity-more loading Transfer of acids from fetal blood to maternal intervillous spaces— maternal Hb more acidic Rt shift—more unloading to fetus…fetal alkalosis shift to left-Hb F more affinity-more loading Pa O2 Hb A Sao2 Hb F Sao2 224075

41. MYOGLOBIN

43. MYOGLOBIN (HIGHER AFFINITY) HYPERBOLIC CURVE –NO COOPERATIVE EFFECT. HYPERBOLIC CURVE –NO COOPERATIVE EFFECT. IF MYO REPLACES ADULT Hb IT NEEDS DOUBLE THE AMOUNT AND WE WILL BE 12 POUNDS HEAVIER. IF MYO REPLACES ADULT Hb IT NEEDS DOUBLE THE AMOUNT AND WE WILL BE 12 POUNDS HEAVIER. BUT THERE(IN MUSCLE) WE NEED A STORAGE SPECIALIST AS ADULT Hb IS TRANSPORT SPECIALIST. BUT THERE(IN MUSCLE) WE NEED A STORAGE SPECIALIST AS ADULT Hb IS TRANSPORT SPECIALIST.

44. OXYGEN FLUX = CARDIAC OUTPUT ×O2 CONTENT ---(MAINLY 1.34 × Hb × SATURATION ) IN A PERIOPERATIVE OR A CRITICAL CARE SETTING MAXIMISE O2 DELIVERY BY MAXIMISING- IN A PERIOPERATIVE OR A CRITICAL CARE SETTING MAXIMISE O2 DELIVERY BY MAXIMISING- 1.CARDIAC OUTPUT. 1.CARDIAC OUTPUT. 2.Hb. 2.Hb. 3.SATURATION. 3.SATURATION.

45. HOPE THIS WOULD BE A VERY HOPE THIS WOULD BE A VERY USEFUL LECTURE USEFUL LECTURE OR ATLEAST A COLOURFUL ONE OR ATLEAST A COLOURFUL ONE

46. THANK YOU