Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 14 Oxygen Dissociation Curve And Its Clinical Importance Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Oxygen hemoglobin dissociation
curve and its clinical importance
Case
? 49-year-old man who was admitted to the department of chest
medicine with dyspnea, weakness and cyanosis in whom differential
diagnosis excluded acute and chronic pulmonary and cardiovascular
disease.
? Saturation measured with a finger pulse oximeter was 89%.
? Despite administration of oxygen through a nasal cannula, saturation
measured with a pulse oximeter did not change.
? Arterial blood gas analysis revealed a saturation of 97.9%, PaO 2 of 102
mm Hg, PaCO2 of 35 mm Hg, HCO3 of 3.4 mmol/l, pH of 7.44.
? Clinical cyanosis and low measured oxygen saturation in the presence
of normal arterial oxygen tension was highly suggestive of
methemoglobinemia ("saturation gap").
? Methemoglobin level, measured at the acute phase of disease was
elevated at 16%. Episode resolved spontaneously.
Saturation Gap
? The "oxygen saturation gap" is the difference between the calculated
oxygen saturation from a standard blood gas machine and the reading
from a pulse oximeter.
? If it is greater than 5%, the patient's hemoglobin may be abnormal,
representing carbon monoxide poisoning, methemoglobinemia, or
sulfhemoglobinemia.
? In present case(97.9%- 89%= 8.9%)
Pulse Oximetry
(measured oxygen saturation
? Pulse oximetry is based on measurement of a ratio of light absorption
by tissues at a red wavelength (660 nm) and at an infrared
wavelength (940 nm).
? OxyHb absorbs infrared and deoxyHb absorbs red light
? Uses empirically derived calibration curves that converts ratio of oxy
to deoxyHb into %saturation.
Calculated oxygen saturation(ABG Machine)
? Calculates % oxygen saturation by following formula
sO2(%) = cHbO2/cHbo2+cHHb
? It is important to note that the denominator in this equation is not
the concentration of total hemoglobin.
? There are two species of hemoglobin present in blood that are
incapable of binding oxygen. They are carboxyhemoglobin (COHb)
and methemoglobin (MetHb)
? In health, COHb and MetHb together comprise less than ~5 % of total
hemoglobin so that, normally, the concentration of total hemoglobin
(ctHb) approximates to the sum of cO 2Hb and cHHb.
? However, there are pathologies ? most notably carbon monoxide
poisoning and methemoglobinemia ? that are associated with a
marked increase in COHb or MetHb, and a resulting marked reduction
in the oxygen-carrying capacity of blood, that is not reflected in sO 2.
This results in "Saturation Gap"
Co-Oximeter
? Many modern blood gas analyzers have an incorporated CO-oximeter
? The measurement is based on spectrophotometric analysis of the
hemoglobin released from a sample of arterial blood
? The four hemoglobin species present in blood (oxyhemoglobin, O 2Hb;
deoxyhemoglobin, HHb; carboxyhemoglobin, COHb; and
methemoglobin, MetHb) each have a characteristic light-absorption
spectrum.
Relationship of O2 saturation with pO2
? A number of environmental factors in blood determine the relative
affinity of hemoglobin for oxygen. The most significant of these
is pO 2.
? Hemoglobin present in blood with relatively high pO 2 has much
greater affinity for oxygen than hemoglobin present in blood with
relatively low pO 2.
? The oxygen dissociation curve (ODC) describes this relationship
graphical y (sO 2 denotes Hb affinity)
Oxygen Hemoglobin Dissociation curve
Although pO 2only reflects a very small proportion (3 %) of the oxygen in
arterial blood, it is highly significant because, as the ODC implies,
it determines the sO 2 and therefore the total amount of oxygen
that is contained in arterial blood for delivery to tissues.
Factors affecting ODC
1. Carbon dioxide
2. Protons (pH)
3. Temperature
4. 2,3 BPG
Increase in any of the above shifts
curve to right and vice-versa
Bohr Effect
? The Bohr effect is decreased affinity of hemoglobin for oxygen with
increase in H+ or CO2
H+
CO2
O2
O2
O2
Importance of Bohr Effect
? Bohr Effect shifts ODC to right
increasing oxygen delivery
Bohr Effect and
Haldane Effect
Methemoglobinemia
(Discussion of case)
? Cyanosis(chocolate cyanosis) with structural y normal heart.
? Important D/D for an acquired or drug induced cause
? Hemoglobin can accept and transport oxygen only when the iron
atom is in its ferrous form
? When haemoglobin becomes oxidized, the iron atom is converted to
the ferric state (Fe3+), resulting in the formation of methemoglobin
? Methemoglobin lacks the electron that is needed to form a bond with
oxygen and thus is incapable of oxygen transport.
? The low level of methemoglobin is maintained through 2 important
mechanisms
1. HMP shunt pathway within the erythrocyte. Through this pathway,
oxidizing agents are reduced by glutathione.
2. Enzyme cytochrome b5 reductase(Methemoglobin reductase) , requires
NADH to reduce methemoglobin to its original ferrous state.
? Any drug that interferes with these mechanisms can lead to
Methemoglobinemia
Conversion Of Methemoglobin To
Hemoglobin is
NADPH+H+ Dependent
H2O2 and Oxidant Drugs
Methemoglobin
Hemoglobin (Fe+2)
(Fe+3)
Methemoglobin Reductase
NADP+
NADPH+ H+
? Congenital Methemoglobinemia
1. arises from globin mutations that Stabilize iron in the ferric state (e.g.
HbM Iwata [87HisTy]
2. from mutations that impair the enzymes that reduce methemoglobin
to hemoglobin (e.g.methemoglobin reductase, NADP diaphorase).
? Acquired Methemoglobinemia is caused by toxins that oxidize heme
iron notably nitrate and nitrite-containing compounds including
drugs commonly used in cardiology and anesthesiology.
Management of Methemoglobinemia
Diagnosis
? Arterial blood with elevated methemoglobin levels has a
characteristic chocolate-brown color(chocolate cyanosis)
? Saturation Gap
Treatment
? Intravenous (IV) methylene blue is the first-line antidotal agent.
? Exchange transfusion and hyperbaric oxygen treatment are second-
line options for patients with severe methemoglobinemia
Therapeutic Induction of Methemoglobin
Formation
? Cyanide competes with cytochrome
oxidase for Fe+++ of methemoglobin to
form cyanmethemoglobin which is
eliminated
? Thereby, the activity of inhibited
cytochrome oxidase is restored.
? Agents used as antidote: sodium nitrite,
amyl nitrite, 4-dimethylaminophenol
Minor Hb
ODC with different types of Hb and Mb
HbF( Fetal Hemoglobin)
? Binding of 2,3-BPG to HbF: weak
? ? Importance
? Residue H21 of the subunit of HbF is Ser rather than His. Since Ser cannot
form a salt bridge, BPG binds more weakly to HbF than to HbA.
? The higher oxygen affinity of HbF facilitates the transfer of oxygen from the
maternal circulation across the placenta to the RBC of the fetus.
HbA1c
ADA Criteria for Diabetes Mel itus
HbA1c > 6.5%
HbA1c
? A1C reflects average glycemia over approximately 3 months and has
strong predictive value for diabetes complications
? A1C testing should be performed routinely in all patients with
diabetes--at initial assessment and as part of continuing care
? Factors affecting HbA1c measurement:
1. Glucose concentration
2. Red cell turnover
3. Analytical Variations
Diabetes Care 2018;41(Suppl. 1):S55?S64
HbA1c
? Variations by Variable Red cell Turnover: hemolytic and other
anemias, recent blood transfusion, use of drugs that stimulate
erythropoesis, end-stage kidney disease, and pregnancy
Methods:
? Ion-exchange high-performance liquid chromatography (HPLC),
? Boronate affinity assay,
? Immunoagglutination
Ref Range: 4-6.2%
Myoglobin
Why is myoglobin unsuitable as an O 2 transport
protein but wel suited for O 2 storage?
S.No Hemoglobin (Hb)
Myoglobin (Mb)
1.
Hb is Oxygen transport protein in Mb is Oxygen storing protein in
RBCs of blood.
muscles.
2.
Tetrameric has four Heme and
Monomeric has one Heme and binds
binds with 4O2
with 1 O2.
3.
Oxygenated at Lungs
Oxygenated at Muscle Cel Cytosol.
4.
HbO2 unloads oxygen at tissues
MbO2 unloads oxygen at cell cytosol
when pO2 is at 40 mmHg.
when pO2 is at 5 mmHg. to rapidly
respiring cells
P50 for HbA1 is 27 torr.
P50 for Mb is 2 torr.
5.
ODC is sigmoid shaped
ODC is hyperbolic shaped.
6.
Hb has 574 amino acids.
Mb has 153 amino acids.
Mol .wt-67,000 Daltons.
Mol wt-17,200 Daltons.
?Thank You!
This post was last modified on 05 April 2022