? 49-year-old man who was admitted to the department of chest
medicine with dyspnea, weakness and cyanosis in whom differential
--- Content provided by FirstRanker.com ---
diagnosis excluded acute and chronic pulmonary and cardiovascular
disease.
--- Content provided by FirstRanker.com ---
? 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
--- Content provided by FirstRanker.com ---
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
--- Content provided by FirstRanker.com ---
of normal arterial oxygen tension was highly suggestive ofmethemoglobinemia ("saturation gap").
? Methemoglobin level, measured at the acute phase of disease was
--- Content provided by FirstRanker.com ---
elevated at 16%. Episode resolved spontaneously.
Saturation Gap
--- Content provided by FirstRanker.com ---
? The "oxygen saturation gap" is the difference between the calculatedoxygen saturation from a standard blood gas machine and the reading
from a pulse oximeter.
--- Content provided by FirstRanker.com ---
? If it is greater than 5%, the patient's hemoglobin may be abnormal,
representing carbon monoxide poisoning, methemoglobinemia, or
--- Content provided by FirstRanker.com ---
sulfhemoglobinemia.? In present case(97.9%- 89%= 8.9%)
Pulse Oximetry
--- Content provided by FirstRanker.com ---
(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
--- Content provided by FirstRanker.com ---
wavelength (940 nm).? OxyHb absorbs infrared and deoxyHb absorbs red light
? Uses empirically derived calibration curves that converts ratio of oxy
--- Content provided by FirstRanker.com ---
to deoxyHb into %saturation.
Calculated oxygen saturation(ABG Machine)
--- Content provided by FirstRanker.com ---
? Calculates % oxygen saturation by following formulasO2(%) = cHbO2/cHbo2+cHHb
? It is important to note that the denominator in this equation is not
--- Content provided by FirstRanker.com ---
the concentration of total hemoglobin.? There are two species of hemoglobin present in blood that are
incapable of binding oxygen. They are carboxyhemoglobin (COHb)
--- Content provided by FirstRanker.com ---
and methemoglobin (MetHb)
? In health, COHb and MetHb together comprise less than ~5 % of total
--- Content provided by FirstRanker.com ---
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
--- Content provided by FirstRanker.com ---
poisoning and methemoglobinemia ? that are associated with a
marked increase in COHb or MetHb, and a resulting marked reduction
--- Content provided by FirstRanker.com ---
in the oxygen-carrying capacity of blood, that is not reflected in sO 2.This results in "Saturation Gap"
Co-Oximeter
--- Content provided by FirstRanker.com ---
? 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
--- Content provided by FirstRanker.com ---
? The four hemoglobin species present in blood (oxyhemoglobin, O 2Hb;
deoxyhemoglobin, HHb; carboxyhemoglobin, COHb; and
--- Content provided by FirstRanker.com ---
methemoglobin, MetHb) each have a characteristic light-absorptionspectrum.
Relationship of O2 saturation with pO2
--- Content provided by FirstRanker.com ---
? A number of environmental factors in blood determine the relativeaffinity of hemoglobin for oxygen. The most significant of these
is pO 2.
--- Content provided by FirstRanker.com ---
? Hemoglobin present in blood with relatively high pO 2 has much
greater affinity for oxygen than hemoglobin present in blood with
--- Content provided by FirstRanker.com ---
relatively low pO 2.? The oxygen dissociation curve (ODC) describes this relationship
graphical y (sO 2 denotes Hb affinity)
--- Content provided by FirstRanker.com ---
Oxygen Hemoglobin Dissociation curveAlthough pO 2only reflects a very small proportion (3 %) of the oxygen in
arterial blood, it is highly significant because, as the ODC implies,
--- Content provided by FirstRanker.com ---
it determines the sO 2 and therefore the total amount of oxygen
that is contained in arterial blood for delivery to tissues.
--- Content provided by FirstRanker.com ---
Factors affecting ODC1. Carbon dioxide
2. Protons (pH)
3. Temperature
--- Content provided by FirstRanker.com ---
4. 2,3 BPGIncrease in any of the above shifts
curve to right and vice-versa
--- Content provided by FirstRanker.com ---
Bohr Effect? The Bohr effect is decreased affinity of hemoglobin for oxygen with
increase in H+ or CO2
--- Content provided by FirstRanker.com ---
H+
CO2
--- Content provided by FirstRanker.com ---
O2O2
O2
--- Content provided by FirstRanker.com ---
Importance of Bohr Effect
? Bohr Effect shifts ODC to right
--- Content provided by FirstRanker.com ---
increasing oxygen deliveryBohr Effect and
Haldane Effect
--- Content provided by FirstRanker.com ---
Methemoglobinemia(Discussion of case)
? Cyanosis(chocolate cyanosis) with structural y normal heart.
? Important D/D for an acquired or drug induced cause
--- Content provided by FirstRanker.com ---
? Hemoglobin can accept and transport oxygen only when the ironatom is in its ferrous form
? When haemoglobin becomes oxidized, the iron atom is converted to
--- Content provided by FirstRanker.com ---
the ferric state (Fe3+), resulting in the formation of methemoglobin
? Methemoglobin lacks the electron that is needed to form a bond with
--- Content provided by FirstRanker.com ---
oxygen and thus is incapable of oxygen transport.? The low level of methemoglobin is maintained through 2 important
mechanisms
--- Content provided by FirstRanker.com ---
1. HMP shunt pathway within the erythrocyte. Through this pathway,oxidizing agents are reduced by glutathione.
2. Enzyme cytochrome b5 reductase(Methemoglobin reductase) , requires
--- Content provided by FirstRanker.com ---
NADH to reduce methemoglobin to its original ferrous state.
? Any drug that interferes with these mechanisms can lead to
--- Content provided by FirstRanker.com ---
MethemoglobinemiaConversion Of Methemoglobin To
Hemoglobin is
--- Content provided by FirstRanker.com ---
NADPH+H+ Dependent
H2O2 and Oxidant Drugs
--- Content provided by FirstRanker.com ---
MethemoglobinHemoglobin (Fe+2)
(Fe+3)
--- Content provided by FirstRanker.com ---
Methemoglobin Reductase
NADP+
--- Content provided by FirstRanker.com ---
NADPH+ H+? Congenital Methemoglobinemia
1. arises from globin mutations that Stabilize iron in the ferric state (e.g.
HbM Iwata [87HisTy]
--- Content provided by FirstRanker.com ---
2. from mutations that impair the enzymes that reduce methemoglobinto hemoglobin (e.g.methemoglobin reductase, NADP diaphorase).
? Acquired Methemoglobinemia is caused by toxins that oxidize heme
--- Content provided by FirstRanker.com ---
iron notably nitrate and nitrite-containing compounds including
drugs commonly used in cardiology and anesthesiology.
--- Content provided by FirstRanker.com ---
Management of MethemoglobinemiaDiagnosis
? Arterial blood with elevated methemoglobin levels has a
--- Content provided by FirstRanker.com ---
characteristic chocolate-brown color(chocolate cyanosis)? Saturation Gap
Treatment
? Intravenous (IV) methylene blue is the first-line antidotal agent.
--- Content provided by FirstRanker.com ---
? Exchange transfusion and hyperbaric oxygen treatment are second-line options for patients with severe methemoglobinemia
Therapeutic Induction of Methemoglobin
--- Content provided by FirstRanker.com ---
Formation? Cyanide competes with cytochrome
oxidase for Fe+++ of methemoglobin to
--- Content provided by FirstRanker.com ---
form cyanmethemoglobin which is
eliminated
--- Content provided by FirstRanker.com ---
? Thereby, the activity of inhibitedcytochrome oxidase is restored.
? Agents used as antidote: sodium nitrite,
--- Content provided by FirstRanker.com ---
amyl nitrite, 4-dimethylaminophenol
Minor Hb
--- Content provided by FirstRanker.com ---
ODC with different types of Hb and MbHbF( Fetal Hemoglobin)
? Binding of 2,3-BPG to HbF: weak
--- Content provided by FirstRanker.com ---
? ? 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.
--- Content provided by FirstRanker.com ---
? The higher oxygen affinity of HbF facilitates the transfer of oxygen from the
maternal circulation across the placenta to the RBC of the fetus.
--- Content provided by FirstRanker.com ---
HbA1cADA Criteria for Diabetes Mel itus
HbA1c > 6.5%
--- Content provided by FirstRanker.com ---
HbA1c? A1C reflects average glycemia over approximately 3 months and has
strong predictive value for diabetes complications
--- Content provided by FirstRanker.com ---
? A1C testing should be performed routinely in all patients with
diabetes--at initial assessment and as part of continuing care
--- Content provided by FirstRanker.com ---
? Factors affecting HbA1c measurement:1. Glucose concentration
2. Red cell turnover
3. Analytical Variations
--- Content provided by FirstRanker.com ---
Diabetes Care 2018;41(Suppl. 1):S55?S64HbA1c
? Variations by Variable Red cell Turnover: hemolytic and other
--- Content provided by FirstRanker.com ---
anemias, recent blood transfusion, use of drugs that stimulateerythropoesis, end-stage kidney disease, and pregnancy
Methods:
--- Content provided by FirstRanker.com ---
? Ion-exchange high-performance liquid chromatography (HPLC),? Boronate affinity assay,
? Immunoagglutination
Ref Range: 4-6.2%
Myoglobin
--- Content provided by FirstRanker.com ---
Why is myoglobin unsuitable as an O 2 transport
protein but wel suited for O 2 storage?
S.No Hemoglobin (Hb)
--- Content provided by FirstRanker.com ---
Myoglobin (Mb)
1.
--- Content provided by FirstRanker.com ---
Hb is Oxygen transport protein in Mb is Oxygen storing protein inRBCs of blood.
muscles.
--- Content provided by FirstRanker.com ---
2.
Tetrameric has four Heme and
--- Content provided by FirstRanker.com ---
Monomeric has one Heme and bindsbinds with 4O2
with 1 O2.
--- Content provided by FirstRanker.com ---
3.
Oxygenated at Lungs
--- Content provided by FirstRanker.com ---
Oxygenated at Muscle Cel Cytosol.4.
HbO2 unloads oxygen at tissues
--- Content provided by FirstRanker.com ---
MbO2 unloads oxygen at cell cytosol
when pO2 is at 40 mmHg.
--- Content provided by FirstRanker.com ---
when pO2 is at 5 mmHg. to rapidlyrespiring cells
P50 for HbA1 is 27 torr.
--- Content provided by FirstRanker.com ---
P50 for Mb is 2 torr.
5.
--- Content provided by FirstRanker.com ---
ODC is sigmoid shapedODC is hyperbolic shaped.
6.
--- Content provided by FirstRanker.com ---
Hb has 574 amino acids.
Mb has 153 amino acids.
--- Content provided by FirstRanker.com ---
Mol .wt-67,000 Daltons.Mol wt-17,200 Daltons.
?Thank You!
--- Content provided by FirstRanker.com ---