Transcript Module E Oxygen Transport and Internal - Macomb

Oxygen Transport and
Internal Respiration
Module E
Chapter 7 Malley
Objectives
• State the formula for calculating oxygen
content.
• Given a PaO2, calculate the amount of
oxygen that is dissolved in plasma in vol%.
• Describe the chemical structure of
hemoglobin.
• Describe the relationship between oxygen
and hemoglobin in the presence of various
factors.
• List the abnormal species of hemoglobin.
• Describe how hypoxia can result from
ineffective cellular utilization of oxygen.
Oxygen Transport
• TWO WAYS TO CARRY OXYGEN
• DISSOLVED IN PLASMA
• COMBINED WITH HEMOGLOBIN
• THE TOTAL AMOUNT OF OXYGEN
PRESENT IS CALLED THE OXYGEN
CONTENT.
• ANY QUESTIONS?
Dissolved Oxygen
• Diffusion occurs because of a partial pressure difference
between alveolus and capillary (gas to liquid).
• The volume of gas that dissolves depends on the
Solubility coefficient of the gas.
• Higher solubility, more dissolved, regardless of partial
pressure.
• O2 dissolved in blood @ 37° C is .003 mL O2/100mL/mm
Hg or
• A normal individual will dissolve between 0.24 and 0.3 mL
of oxygen/mL of blood at one atmosphere and 37° C.
• Dissolved O2 (PaO2) represents 0.3 vol%
• Linear relationship between PaO2 and the volume of
oxygen dissolved
• 0.3 vol% at 100mmHg PaO2, 0.6 vol% at 200 mmHg PaO2
Dissolved Oxygen – PaO2
• PaO2 does not tell us how much oxygen is in the
blood.
• Tells us about the potential driving pressure at a later
point, but the volume (vol%) is the key issue.
• Determined by PAO2, / relationships, level of
ventilation and the AC membrane.
• THINK ABOUT THE CAUSES OF HYPOXEMIA!
Combined O2
• Dissolved oxygen is inadequate for
metabolic needs.
• Need a substance which will bind to
oxygen and carry it, BUT will release it
when needed.
• Voila! Hemoglobin!
• Miracle #2…Hemoglobin also carries carbon
dioxide and is a key buffer of [H+].
Hemoglobin
• Hemoglobin is composed of two groups:
• Heme Group – Primarily iron in the Fe+2
(ferrous) state.
• Globulin – 4 amino acid chains;
• 2 alpha chains made up of 141 amino acids,
• 2 beta chains made up of 146 amino acids.
• Large molecule – GMW of 64,500 g.
• One heme group binds with one of the amino
acid chains and oxygen binds with the iron in
the heme group in a reversible way.
O2 + Fe+2 FeO2
Hemoglobin & the RBC
• “Normal” hemoglobin level
• 15 g/dl (men) & 13-14 g/dl (women) - Malley
• 15 + 1.5 g/dl (men) & 13.5 + 1.5 g/dl (women) – Egan
• 15 + 2 (men) & 14 + 2 (women) - Easy
• Why do women have less?
• The hemoglobin molecule resides in the
erythrocyte and is responsible for giving the
blood its red color.
• Hundreds of hemoglobin variants.
• Normal: A, A2, F
• Abnormal: S, H
Combined Oxygen
• The affinity of hemoglobin for oxygen
increases with each oxygen molecule
attached
• “All or Nothing”
• Each gram of Hemoglobin combines with
1.34 mL of oxygen.
• Oxygen Saturation only talks about how
much hemoglobin is saturated, NOT how
much hemoglobin is present.
Oxygen Saturation
• Saturation = Sites Filled
Total Sites Available
• Example:
• 80 sites filled
= 80% saturation
100 sites available
Oxyhemoglobin Curve
There is a direct (BUT
NOT LINEAR)
relationship between
the dissolved oxygen
in the blood (PO2) and
the amount of oxygen
that attaches to the
hemoglobin (SO2).
PO2
SO2
27
50
40
75
60
90
250
100
Significance of OHDC Shape
• The steep line signifies that a small change in
PO2 will yield a large change in SO2.
• This is the dissociation portion of the curve.
• Oxygen release is maximized.
• A large amount of oxygen can be delivered to the tissues in
times of compromised cardiovascular function or increased
demands.
• COPD patients “live” on the steep portion, small changes in
PaO2 will yield greater changes in SaO2.
• The flat line signifies that a large change in PO2
results in only a minimal increase in SO2.
• This is the association portion of the curve.
• Oxygen carrying is maximized.
• The PO2 has to fall below 60 mm Hg before saturation
becomes significantly affected.
• Aging, High Altitudes
P50
• The specific affinity of oxygen for
hemoglobin can be assessed by
evaluating at what PO2 there is a 50%
SO2.
• It is measured at 37° C, a PaCO2 40 mm
Hg, pH 7.40.
• Normal value is 27 mm Hg (25-27 mm
Hg)
• As P50 changes, we say the “curve has
shifted”.
Shifts in the OHDC
• Left Shift
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Increased oxygen affinity for hemoglobin.
This is the expected shift at the lungs (Left-Lungs)
For any given PO2, SO2 will be higher.
Decreasing P50
• Right Shift
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Decreased oxygen affinity for hemoglobin.
This is the expected shift at the tissues.
For any given PO2, SO2 will be lower.
Increasing P50
Bohr Effect
• The effect of CO2 on the OHDC is known as the
Bohr Effect. (OH – Bohr)
• High PCO2 levels and low pH decrease affinity
of hemoglobin for oxygen (a right-ward shift)
• This occurs at the tissues where a high level of PCO2
and acidemia contribute to the unloading of oxygen
(and the attachment of CO2 to the unbound
hemoglobin).
• At the lungs, the high levels of oxygen facilitate the
release of CO2 from the Hemoglobin molecule. This
is known as the Haldane Effect.
2,3 DPG
• 2,3 DPG is an organic phosphate normally found in RBC,
that has a tendency to bind with Hemoglobin and thereby
decrease the affinity of Hemoglobin for oxygen.
• It promotes a rightward shift and enhances oxygen
unloading at the tissues. This shift is longer in duration
than that due to [H+], PCO2 or temperature.
• A doubling of DPG will result in a 10 torr increase in P50.
• The levels increase with cellular hypoxia.
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Anemia
Hypoxemia secondary to COPD.
Congenital Heart Disease
Ascent to high altitudes
• The levels are reduced with
• Septic Shock
• Acidemia
• STORED BLOOD in ACD: NO DPG after 2 weeks of storage.
Oxygen Content
• The total amount of oxygen present in the blood.
• CaO2 = (Hb * 1.34 * SaO2) + ( PaO2 * 0.003)
• C
O2
= (Hb * 1.34 * S O2) + ( P O2 * 0.003)
• The difference between the two (C(a- )O2) is
approximately 5 vol%.
• The Fick equation describes the relationship
between the cardiac output, the oxygen
consumption and the C(a- )O2.
• CO * C(a- )O2 =
O2
• 5,000 mL/min * 5 mL O2/100 ml = 250 mL O2/min
Cyanosis
• A clinical condition manifested by a bluish discoloration
of the mucous membranes or nail beds.
• Peripheral vs. Central
• Present when 5 g/dl of hemoglobin is desaturated.
• This usually correlates with a SaO2 below
85%.
• Calculated as follows:
[(Hb * Arterial Desaturation) + (Hb * Venous
Desaturation)] /2
• Normal Arterial Desaturation is 100% - 98% or 2%.
• Normal Venous Desaturation is 100% - 75% or 25%.
[(15 * .02) + (15 * .25)] /2 = [.3 +3.75] / 2 = 4.05/2 =
2.025g%
• ANEMIC PATIENTS WILL NEVER BE CYANOTIC!
Oxygen Transport
• The volume of oxygen leaving the left
ventricle each minute.
• CaO2 * CO = 20 ml O2/100 mL * 5,000
mL/min
• 1,000 mL O2 / min
• If oxygen consumption is 250 mL O2 / min, then
we “extract” 25% of the total.
• This can also be determined by dividing the
C(a- )O2 by the CaO2. (5 vol% / 20 vol%) = .25
• Key factors are the PaO2, SaO2, SV, & HR
Hemoglobin Abnormalities
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Carboxyhemoglobin
Sulfhemoglobin
Fetal Hemoglobin
Methemoglobin
Hemoglobin S
Carboxyhemoglobin
• Carbon Monoxide has 245 times the affinity for
hemoglobin as oxygen.
• Causes a leftward shift (increased affinity of Oxygen)
• Normal level is less than 3%
• 10% is common with smokers.
• Toxic at 20%; Lethal at 50%.
• Venous HbCO = Arterial HbCO (Ann Emerg Med. 1995
Apr;25(4):481-3)
• Suspect incomplete combustion if level is elevated.
• Furnace, space heater
• Treatment is 100% oxygen
• Reduces half-life of HbCO from 5 hours to 20 minutes.
• Hyperbaric treatment remains controversial.
Methemoglobin
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A normal variant of adult hemoglobin.
Ferrous to Ferric (loses an electron, Fe+3)
Normal levels are less than 1%.
Usually associated with excessive nitrate
ingestion.
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Amyl Nitrate
Nitroglycerine
Nipride
Topical anesthetics
• Blood will appear rusty or brown in color.
• Treatment with methylene blue
Sulfhemoglobin
• Sulfhemoglobin results from the union of
hemoglobin with medications such as
phenacetin (sedative no longer used) or
sulfonamides (antibiotics including Bactrim
& Septra).
• The resultant form of hemoglobin is unable
to transport oxygen, and is untreatable.
• The only treatment is to wait until the
affected red blood cells are destroyed as
part of their normal life cycle.
Fetal Hemoglobin (HbF)
• Fetal hemoglobin (hemoglobin F) is the main
hemoglobin that transports oxygen around the
body of the developing baby during the last 7
months of pregnancy.
• It has a greater affinity for oxygen than
Hemoglobin A (P50 of 20 mm Hg).
• At about 30 weeks gestation, the fetus begins to
make increasing amounts of hemoglobin A.
• Hemoglobin F does not turn into hemoglobin A.
• As they grow babies automatically turn off the
production of hemoglobin F (usually complete by
one year). Failure to stop Hemoglobin F
production is found in certain beta thalassemias.
Possible link to SIDS.
Hemoglobin S
• Hemoglobin S is a abnormal
variant of Hemoglobin A where
one of the 146 amino acids in
the beta chain is altered.
• Inherited disorder from both
parents.
• 1% of African Americans.
• Recurrent painful episodes
(Crisis) occur as sickled cells
become obstructed.
• Typical “anemic” symptoms.
• Can lead to infections and
stroke.