2. GAS TRANSPORT
• Blood transports Oxygen and Carbon
dioxide between lungs and the tissues of
the body
• These gases are transported in different
states
1. Dissolved in plasma
2. Chemically combined with hemoglobin
3. Converted to a different molecule
3.
4. • 98% of LA blood- pulmonary cir-104 mm
of Hg
• 2% bronchial cir( SYSTEMIC CIR FROM
AORTA)- 40 mm of Hg
• “shunt flow,”-venous admixture of blood
causes the Po2 of the blood entering the left
heart and pumped into the aorta to fall to
about 95 mm Hg
5.
6.
7. Oxygen Transport
• Due to low solubility,
only 3% of oxygen is
dissolved in plasma
• 97% of oxygen combines
with hemoglobin
8.
9. • Each Hb consists of a globin portion composed of 4
polypeptide chains
• Each Hb also contains 4 iron containing pigments called
heme groups
• Up to 4 molecules of O2 can bind one Hb molecule
because each iron atom can bind one oxygen molecule
• There are about 250 million Hb hemoglobin molecules
in one Red Blood Cell
• When 4 oxygen molecules are bound to Hb, it is 100%
saturated, with fewer, it is partially saturated
• Oxygen binding occurs in response to high partial
pressure of Oxygen in the lungs
10. • Oxygen + Hb Oxyhemoglobin (Reversible)
• Cooperative binding Hb’s affinity for O2
increases as its saturation increases (similarly its
affinity decreases when saturation decreases)
• In the lungs where the partial pressure of oxygen
is high, the rxn proceeds to the right forming
Oxyhemoglobin
• In the tissues where the partial pressure of oxygen
is low, the rxn reverses. OxyHb will release
oxygen, forming again Hb (or properly said
deoxyhemoglobin)
11.
12. Oxygen-Hemoglobin Dissociation Curve
• Hb saturation is determined by the partial
pressure of Oxygen
• @ High partial pressures of O2 – lungs – Hb is
98% saturated
• @ Low partial pressures of Oxygen – tissues –
Hb is only 75% saturated
• “S” shape is a trademark of its cooperative
binding interaction – the binding of one oxygen
molecule increases Hb’s affinity for binding
additional oxygen molecules
13. Other factors altering Hb saturation
• Low pH (Carbonic Acid, Lactic Acid)
• High Temperature
• High 2,3 DiphosphoGlycerate concentration
(DPG)
• High partial pressure of Carbon Dioxide
• These conditions decrease Hb’s affinity for
oxygen, releasing more oxygen to active cells
14. • Example: Vigorous physical exercise
• Contracting muscles produce metabolic acids such as
lactic acid which lower the pH, more heat and more
carbon dioxide.
• In addition 2,3 DPGA is produced during conditions of
higher temperature and lower partial pressures of oxygen
Acting together or individually, these
conditions lead to a decrease in
Hemoglobin’s activity for Oxygen,
releasing more Oxygen to the tissues
(muscles)
15. • 2,3-BPG is very plentiful in red cells. It is
formed from 3-phosphoglyceraldehyde,
which is a product of glycolysis via the
Embden–Meyerhof pathway .
• It is a highly charged anion that binds to the
chains of deoxyhemoglobin. One mole of
deoxyhemoglobin binds 1 mol of 2,3-BPG.
16. • 2,3-DPG is a small molecule that binds
to a specific site on hemoglobin, called
the allosteric site, and reduces its
affinity for oxygen.
19. • The decrease in O2 affinity of hemoglobin
when the pH of blood falls is called the
Bohr effect ..
20. • SHIFT to the RIGHT
• Decreased affinity of Hb for Oxygen
• Increased delivery of Oxygen to tissues
• It is brought about by
1. Increased partial pressure of Carbon Dioxide
2. Lower pH (high [H+])
3. Increased temperature
4. Increased levels of 2,3 DPGA
• Ex: increased physical activity, high body
temperature (hot weather as well), tissue
hypoxia (lack of O2 in tissues)
21. • SHIFT to the LEFT
• Increased affinity of Hb for Oxygen
• Decreased delivery of Oxygen to tissues
• It is brought about by
1. Decreased partial pressure of Carbon Dioxide
2. Higher pH (low [H+])
3. Decreased temperature
4. Decreased levels of 2,3 DPGA
• Ex: decreased physical activity, low body
temperature (cold weather as well), satisfactory
tissue oxygenation
22.
23. • 100% O2 (PO2 = 760 mm Hg), the normal
hemoglobin becomes 100% saturated
• When fully saturated, each gram of normal
hemoglobin contains 1.39 mL of O2.
However, blood normally contains small
amounts of inactive hemoglobin derivatives,
and the measured value in vivo is lower.
The traditional figure is 1.34 mL of O2.
24. • The hemoglobin concentration in normal
blood is about 15 g/dL (14 g/dL in women
and 16 g/dL in men). Therefore, 1 dL of
blood contains 20.1 mL (1.34 mL x 15) of
O2 bound to hemoglobin when the
hemoglobin is 100% saturated. The amount
of dissolved O2 is a linear function of the
PO2 (0.003 mL/dL blood/mm Hg PO2).
25. • Therefore, 15 times 1.34 equals 20.1, which
means that, on average, the 15 grams of
hemoglobin in 100 milliliters of blood can
combine with a total of almost exactly 20
milliliters of oxygen if the hemoglobin is
100 per cent saturated.
26. • P O2 – 95MM OF HG The arterial blood
therefore contains a total of about 19.8 mL
of O2 per dL: 0.29 mL in solution and 19.5
mL bound to hemoglobin. In venous blood
at rest, the hemoglobin is 75% saturated and
the total O2 content is about 15.2 mL/dL:
0.12 mL in solution and 15.1 mL bound to
hemoglobin.
27. • Thus, at rest the tissues remove about 4.6
mL of O2 from each deciliter of blood
passing through them
28. Myoglobin
• Myoglobin is an iron-containing pigment
found in skeletal muscle. It resembles
hemoglobin but binds 1 rather than 4 mol of
O2 per mole. Its dissociation curve is a
rectangular hyperbola rather than a sigmoid
curve.
29. • Because its curve is to the left of the
hemoglobin curve it takes up O2 from
hemoglobin in the blood. It releases O2 only
at low PO2 values, but the PO2 in exercising
muscle is close to zero.
30. • The myoglobin content is greatest in
muscles specialized for sustained
contraction. The muscle blood supply is
compressed during such contractions, and
myoglobin may provide O2 when blood
flow is cut off.
31. Combination of Hemoglobin with
Carbon Monoxide—Displacement
of Oxygen
• Carbon monoxide combines with
hemoglobin at the same point on the
hemoglobin molecule as does oxygen;it can
therefore displace oxygen from the
hemoglobin, thereby decreasing the oxygen
carrying capacity of blood.
• Further, it binds with about 250 times as
much tenacity as oxygen.
32. Carbon Dioxide Transport
• Produced by cells thru-out the body
• CO2 diffuses from tissue cells and into the
capillaries
• 7% dissolves in plasma
• 93% diffuses into the Red Blood Cells
• Within the RBC ~23% combines with Hb (to
form carbamino hemoglobin) and ~ 70% is
converted to Bicarbonate Ions which are then
transported in the plasma
33. • In the lungs, which have low Carbon Dioxide partial
pressure, CO2 dissociates from CarbaminoHemoglobin,
diffuses back into lungs and is exhaled
• Within the RBC, CO2 combines with water and in the
presence of carbonic anhydrase it transforms into
Carbonic acid
• Carbonic acid then dissociate into H+ and HCO3-
• In the lungs CO2 diffuses out into the alveoli. This
lowers the partial press. Of Co2 in blood, causing the
chemical reactions to reverse
35. • Other gases have different affinities for hemoglobin
36. • CO carbon monoxide has more than 250 times the
affinity for Hb than oxygen. It will quickly and
almost irreversibly bind to Hb CO poisoning
• NO nitrogen oxide has more than 200,000 times
the affinity for Hb than oxygen. Irreversible bind
• CO and O2 bind to same site on Hb
• CO2 and O2 bind to different sites on Hb
• Myoglobin (in muscle cells) binds more tightly to
oxygen than Hb but NOT cooperatively (Mb
serves as temporary intracellular O2 storage
mechanism useful in muscle contraction)
37.
38. Llama and Vicuna
• Llama & Vicuna live in
the Andes Mts. South
America
• Oxygen dissociation
curves are located to the
left of other mammals
• Higher oxygen affinity
of the blood of these
animals aids in oxygen
uptake at the low
pressure of high altitude
39. High Altitude Adaptations for us…
• Chronic Mountain Sickness (ventilatory
depression, polycythemia, heart failure) R.I.P.
• At high altitude initially the person is
hyperventilating
• After some time however…
• Hb/RBC production increases (more oxygen
carrying capacity)
• 2,3 DPGA concentration rises in RBCs shifting
the curve to the right, improving O2 tissue
delivery
• Increased sensitivity to concentrations of [H+],
CO2, pH and their respective variations
40. That’s exactly why sportsmen (real
football players for instance-
wrongfully called “soccer players”
here) train in the mountains
To improve physical performance
!
41. • At similar pH and Co2, small mammals have lower
oxygen affinity. Improved delivery of oxygen in the
tissues to sustain the high metabolic rate of a small animal
42. • Higher oxygen
affinity of the fetal
blood helps in the
transfer of oxygen to
the fetal blood in the
placenta
• Fetus – higher
affinity- shift left
• Fetus [Hb]~200g/L
• Mother [Hb]~135g/L
• Normal [Hb]~150g/L
43. Control of Respiration
• Basic rhythm is controlled by respiratory centers
located in medulla and brainstem
• An inspiratory center sends impulses via nerves to the
effectors: diaphragm and intercostals muscles
• Normal breathing rate @ rest is about 12 to 15 breaths a
minute
• Chemo receptors located thru out the body modify the
breathing rhythm by responding to changes in partial
pressures of Co2, O2, pH.
• Central chemoreceptors medulla changes in pH
• Peripheral chemoreceptors: carotid body, aortic bodies
monitor values of arterial blood: Pco2, Po2, pH
44.
45. Carbon dioxide is the most important factor
controlling depth and rate of breathing
For all other inquiries, please refer back to the BOHR Effect.
46. • HYPERVENTILATION
• Increased rate and depth
of breathing if
• Low pp. O2
• High pp. CO2
• Low pH, High [H+]
• High Temperature
• High 2,3 DPGA
• High metabolic
requirements
• Shift to the RIGHT
• HYPOVENTILATION
• Decreased rate and depth
of breathing if
• High pp O2
• Low pp CO2
• High pH, Low [H+]
• Low Temperature
• Low 2,3 DPGA
• Low metabolic
requirements
• Shift to the LEFT
47. Other factors that affect respiration
• Pain & strong emotion
• Pulmonary Irritants (dust, smoke, noxious fumes, excess
mucus)
• Voluntary control (ALWAYS OVERIDDEN)
• Lung Hyperinflation (stretch receptors in pleurae send
inhibitory signals protecting against hyperinflation)
• Exercise and ventilation