1. GAS TRANSPORT & CONTROL OF RESPIRATION

2. GAS TRANSPORT
Blood transports Oxygen and Carbon dioxide between lungs and the tissues of the body
These gases are transported in different states
Dissolved in plasma
Chemically combined with hemoglobin
Converted to a different molecule

3. Oxygen Transport
Due to low solubility, only 1.5 % of oxygen is dissolved in plasma
98.5 % of oxygen combines with hemoglobin

5. 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

6. 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)

8. 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

9. 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

10. 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)

11. BOHR EFFECT

12. Bohr Effect
Bohr Effect refers to the changes in the affinity of Hemoglobin for oxygen
It is represented by shifts in the Hb-O2 dissociation curve
Three curves are shown with progressively decreasing oxygen affinity indicated by increasing P(50)

13. SHIFT to the RIGHT
Decreased affinity of Hb for Oxygen
Increased delivery of Oxygen to tissues
It is brought about by
Increased partial pressure of Carbon Dioxide
Lower pH (high [H+])
Increased temperature
Increased levels of 2,3 DPGA
Ex: increased physical activity, high body temperature (hot weather as well), tissue hypoxia (lack of O2 in tissues)

14. SHIFT to the LEFT
Increased affinity of Hb for Oxygen
Decreased delivery of Oxygen to tissues
It is brought about by
Decreased partial pressure of Carbon Dioxide
Higher pH (low [H+])
Decreased temperature
Decreased levels of 2,3 DPGA
Ex: decreased physical activity, low body temperature (cold weather as well), satisfactory tissue oxygenation

16. 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

17. 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

18. Other gases have different affinities for hemoglobin

19. 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)

21. 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

22. 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

23. That’s exactly why sportsmen (real football players for instance- wrongfully called “soccer players” here) train in the mountains To improve physical performance !

24. At similar pH and Co2, small mammals have lower oxygen affinity
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

25. 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

26. 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 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

28. Carbon dioxide is the most important factor controlling depth and rate of breathing
For all other inquiries, please refer back to the BOHR Effect.

29. 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

30. 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