OXYHEMOGLOBIN OXYHEMOGLOBIN DISSOCIATION CURVEDISSOCIATION CURVE

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

HOPE THIS WOULD BE A VERY HOPE THIS WOULD BE A VERY USEFUL LECTURE USEFUL LECTURE

OR ATLEAST IT WILL BE A OR ATLEAST IT WILL BE A ---------FUL LECTURE---------FUL LECTURE

ANAESTHETISTS DO ANAESTHETISTS DO PREANAESTHETIC CHECK UP PREANAESTHETIC CHECK UP

What is important ?? What is important ??

LAVOISIER AND LAPLACE LAVOISIER AND LAPLACE 17791779 INTAKE OF SOME GASES WAS INTAKE OF SOME GASES WAS

RESPIRATION AND IT PRODUCED RESPIRATION AND IT PRODUCED SOME ACID SOME ACID

OXYOXY= ACID= ACID GENGENE= PRODUCER. E= PRODUCER.

ATMOSPHERIC AIR ATMOSPHERIC AIR NITROGEN = 78%NITROGEN = 78% OXYGEN = 21%OXYGEN = 21% ARGON = 0.9%ARGON = 0.9% CO CO 22 = 0.03% = 0.03% TRACES OF HELIUM ,NEON AND TRACES OF HELIUM ,NEON AND

KRYPTONKRYPTON

BAROMETRIC PRESSURE BAROMETRIC PRESSURE PPBB= 760 mm Hg = 760 mm Hg 760 760 × 21/100 =× 21/100 =160 mm Hg160 mm Hg.. (P(PBB × Fio2) × Fio2)HUMIDIFIED IN THE AIRWAYS.HUMIDIFIED IN THE AIRWAYS.P H2O = 47 mmHg.P H2O = 47 mmHg.PIO2 = (760-47) × 21/100 = PIO2 = (760-47) × 21/100 = 150 mmHg150 mmHg..

ALVEOLUS -- CO2 DILUTESALVEOLUS -- CO2 DILUTESPA0PA022 = PIO = PIO22 – PACO – PACO22 / RQ / RQ

= 150 - 45 = = 150 - 45 = 105 105

RQ = RESPIRATORY QUOTIENT RQ = RESPIRATORY QUOTIENT COCO2 2 PRODUCED / OPRODUCED / O22 CONSUMED CONSUMED

ALVEOLUSALVEOLUS ↓ ↓ OO22 PLASMAPLASMA ↓ ↓ OO22 DISSOLVED OXYGENDISSOLVED OXYGEN ↓ ↓ TRANSFERRED TO HbTRANSFERRED TO Hb

Pa Pa OO2 2 100 mm Hg100 mm Hg

160 -150-105-100- 40-25-4160 -150-105-100- 40-25-4 oxygen cascade oxygen cascade

OXYGEN CARRIAGE IN OXYGEN CARRIAGE IN TWO FORMSTWO FORMS DISSOLVED — DISSOLVED — 0.3 ml / 100ml0.3 ml / 100ml Very less but.,Very less but., IT IS IT IS IMPORTANTIMPORTANT

– IT DETERMINES PaO2IT DETERMINES PaO2– IT TRANSFERS O2 TO IT TRANSFERS O2 TO

HAEMOGLOBIN.HAEMOGLOBIN.– IT IS THIS SMALL QUANTITY WHICH IT IS THIS SMALL QUANTITY WHICH

DIFFUSES TO TISSUES FIRST.DIFFUSES TO TISSUES FIRST.

HEMOGLOBIN HEMOGLOBIN

1 gm of Hb carries 1.34 ml-1.39 ml of 1 gm of Hb carries 1.34 ml-1.39 ml of OO22

19.5-19.7 ml oxygen / 100 ml 19.5-19.7 ml oxygen / 100 ml Dissolved + Hb oxygen= 20 mlDissolved + Hb oxygen= 20 ml 200 ml / litre or 200 ml / litre or 1000 ml / 5 litre1000 ml / 5 litre

1000 ml 1000 ml oo2 2 supplied supplied 250 ml consumed 250 ml consumed 750 ml returned 750 ml returned SvO2 75%SvO2 75% Oxygen flux = Oxygen flux = CARDIAC OUTPUT CARDIAC OUTPUT

× 1.34 × Hb × × 1.34 × Hb × SATURATIONSATURATION

HEMOGLOBIN= HEMOGLOBIN= HEMEHEME+GLOBIN+GLOBIN FOURFOUR HEME MOLECULES +GLOBIN HEME MOLECULES +GLOBIN

(FOUR CHAINS )(FOUR CHAINS ) 2 ALPHA AND 2 BETA CHAINS.2 ALPHA AND 2 BETA CHAINS. FOUR HEMES FOUR HEMES

(FERROPROTOPORPHYRIN ) CAN (FERROPROTOPORPHYRIN ) CAN ATTACH 4 OXYGEN MOLECULESATTACH 4 OXYGEN MOLECULES

O2 + FERROUS = FERRIC O2 + FERROUS = FERRIC → → SATURATION → OXYGENATED HbSATURATION → OXYGENATED Hb

COOPERATIVE EFFECT.COOPERATIVE EFFECT.

OXYGEN ENTRY TO Hb PROMOTES OXYGEN ENTRY TO Hb PROMOTES FURTHER ENTRY BY INCREASING THE FURTHER ENTRY BY INCREASING THE AFFINITY UPTO 500 TIMES TO SUCK MORE AFFINITY UPTO 500 TIMES TO SUCK MORE O2----O2----POSITIVE COOPERATIVE EFFECT.POSITIVE COOPERATIVE EFFECT.

IN DOWNLOADING IN TISSUES. REVERSE IN DOWNLOADING IN TISSUES. REVERSE IS IS NEGATIVE COOPERATIVE EFFECTNEGATIVE COOPERATIVE EFFECT

Parrots and parents Parrots and parents Hemoglobin and oxygen act a little like Hemoglobin and oxygen act a little like

parents and children. When all are living at parents and children. When all are living at home (i.e. hemoglobin is fully saturated) home (i.e. hemoglobin is fully saturated) then the parents don’t want any to leave:then the parents don’t want any to leave:

but once one has flown the nest (i.e. but once one has flown the nest (i.e. dissociated from hemoglobin) – parents dissociated from hemoglobin) – parents find it progressively easier to let go. find it progressively easier to let go.

What this means that the conformation of What this means that the conformation of the hemoglobin molecule depends on the the hemoglobin molecule depends on the number of molecules bound: number of molecules bound:

as one molecule of oxygen becomes as one molecule of oxygen becomes unbound, the affinity for the others falls unbound, the affinity for the others falls [and vice-versa].[and vice-versa].

This is represented by the oxyhemoglobin This is represented by the oxyhemoglobin dissociation curve.dissociation curve.

Why the curve is sigmoid Why the curve is sigmoid ????

COOPERATIVE EFFECT CAUSES THE COOPERATIVE EFFECT CAUSES THE CURVE TO BE SIGMOID.CURVE TO BE SIGMOID.

RR FORM (RELAXED) –OXYGENATED FORM (RELAXED) –OXYGENATED T T FORM (TAUT) - DE OXYGENATED FORM (TAUT) - DE OXYGENATED

BEFORE THE CURVE – A BEFORE THE CURVE – A BREAKBREAK

A LADY PATIENT ENTERED A A LADY PATIENT ENTERED A DOCTOR’S (MALE) CABIN AND SAIDDOCTOR’S (MALE) CABIN AND SAID

“ “ SIR, CAN I ASK MY HUSBAND SIR, CAN I ASK MY HUSBAND ALSO TO COME INSIDE.”ALSO TO COME INSIDE.”

DOCTOR : DOCTOR : “ BELIEVE ME, I AM A “ BELIEVE ME, I AM A GENTLEMANGENTLEMAN.”.”

LADY PATIENT : LADY PATIENT : ““SIR I BELIEVE YOU ., BUT I SIR I BELIEVE YOU ., BUT I

DON’T BELIEVE MY DON’T BELIEVE MY HUSBAND AND YOUR HUSBAND AND YOUR NURSE OUTSIDE”NURSE OUTSIDE”

CURVE OF PaO2 TO SaO2 CURVE OF PaO2 TO SaO2 PaO2 SaO2

27 50 (P50)

40 75 (VENOUS)

60 90

100 98

P 50 = 27 , Rt and left P 50 = 27 , Rt and left

SHIFT TO RIGHT = PSHIFT TO RIGHT = P5050 > 27 > 27 SHIFT TO LEFT= PSHIFT TO LEFT= P5050 < 27 < 27 RIGHT SHIFT RIGHT SHIFT AT ANY PaO2 LESS AT ANY PaO2 LESS

AFFINITY ,LESS SATURATIONAFFINITY ,LESS SATURATIONINCREASED H + IONS (ACID)INCREASED H + IONS (ACID)INCREASED PCO2,INCREASED PCO2,INCREASED TEMPINCREASED TEMPINCREASED 2-3 DPGINCREASED 2-3 DPG

BOHR EFFECTBOHR EFFECT

↑ ↑ PCO2 AND ACIDOSIS CAUSE RT. PCO2 AND ACIDOSIS CAUSE RT. SHIFTSHIFT

H + IONS BIND TO GLOBIN CHAINS H + IONS BIND TO GLOBIN CHAINS TO EFFECT A CONFORMATIONAL TO EFFECT A CONFORMATIONAL CHANGE IN HEME ATTACHMENT CHANGE IN HEME ATTACHMENT FAVOURING UNLOADING OF OFAVOURING UNLOADING OF O22 ( WE ( WE WANT TO HAPPEN IN TISSUES.)WANT TO HAPPEN IN TISSUES.)

HALDANE EFFECTHALDANE EFFECT

DEOXYGENATED BLOOD DEOXYGENATED BLOOD CAN PICK UP MORE COCAN PICK UP MORE CO22

THINK OF TISSUES : THINK OF TISSUES : UNLOADING O2UNLOADING O2→ → DEOXYGENATED DEOXYGENATED

BLOOD BLOOD → PICKS UP MORE CO2→ PICKS UP MORE CO2

15 DAYS OLD BLOOD CAN 15 DAYS OLD BLOOD CAN CAUSE DECREASED 2-3 DPG CAUSE DECREASED 2-3 DPG LEVELS TO SHIFT LEFT--LESS LEVELS TO SHIFT LEFT--LESS UNLOADING AND MORE UNLOADING AND MORE AFFINITY (KENNEDY EFFECT)AFFINITY (KENNEDY EFFECT)

24-48 HOURS TO BECOME 24-48 HOURS TO BECOME NORMAL.NORMAL.

What is the role of 2-3 What is the role of 2-3 DPG ??DPG ??

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

Useful increase in 2-3 Useful increase in 2-3 BPGBPG HIGH ALTITUDE.HIGH ALTITUDE. COPDCOPD CYANOTIC HEART DISEASECYANOTIC HEART DISEASE SEVERE ANEMIAS.SEVERE ANEMIAS.

FETAL HbFETAL Hb

Fetal Hb (higher affinity)Fetal Hb (higher affinity) Umbilical venous blood Umbilical venous blood

(20-25 mmHg O2)(20-25 mmHg O2) DOUBLE BOHR EFFECTDOUBLE BOHR EFFECT Transfer of acids from Transfer of acids from

fetal blood to maternal fetal blood to maternal intervillous spaces—intervillous spaces—maternal Hb more acidic maternal Hb more acidic Rt shift—more unloading Rt shift—more unloading to fetus…fetal alkalosis to fetus…fetal alkalosis shift to left-Hb F more shift to left-Hb F more affinity-more loading affinity-more loading

PaO2

Hb ASao2

Hb F Sao2

22 40 75

MYOGLOBINMYOGLOBIN

MYOGLOBIN (HIGHER MYOGLOBIN (HIGHER AFFINITY)AFFINITY) HYPERBOLIC CURVE –NO HYPERBOLIC CURVE –NO

COOPERATIVE EFFECT. COOPERATIVE EFFECT. IF MYO REPLACES ADULT Hb IT IF MYO REPLACES ADULT Hb IT

NEEDS DOUBLE THE AMOUNT AND NEEDS DOUBLE THE AMOUNT AND WE WILL BE WE WILL BE 12 POUNDS HEAVIER12 POUNDS HEAVIER. .

BUT THERE(IN MUSCLE) WE NEED BUT THERE(IN MUSCLE) WE NEED A STORAGE SPECIALIST AS ADULT A STORAGE SPECIALIST AS ADULT Hb IS TRANSPORT SPECIALIST.Hb IS TRANSPORT SPECIALIST.

OXYGEN FLUX = CARDIAC OXYGEN FLUX = CARDIAC OUTPUT OUTPUT ×O2 CONTENT ---×O2 CONTENT ---((MAINLY 1.34 MAINLY 1.34 × Hb × × Hb × SATURATIONSATURATION ) ) IN A PERIOPERATIVE OR A IN A PERIOPERATIVE OR A

CRITICAL CARE SETTING CRITICAL CARE SETTING MAXIMISE O2 DELIVERY BY MAXIMISE O2 DELIVERY BY MAXIMISING-MAXIMISING-

1.CARDIAC OUTPUT.1.CARDIAC OUTPUT. 2.Hb.2.Hb. 3.SATURATION.3.SATURATION.

HOPE THIS WOULD BE A VERY HOPE THIS WOULD BE A VERY USEFUL LECTURE USEFUL LECTURE

OR ATLEAST A OR ATLEAST A CCOOLLOOUURRFFUULL ONEONE

THANK YOUTHANK YOU