Friday, May 28, 2021

Physiology of Transport of Gases | Gas Exchange

GAS EXCHANGE


SITES OF GAS EXCHANGE 


It occurs in two places mainly 

       -At tissues

(between blood & tissues).

       -At the lungs

(between blood & air).


MECHANISM OF GAS EXCHANGE


Gaseous exchange occurs by simple diffusion.


SIMPLE DIFFUSION


The movement of gases occur down the partial pressure gradient i.e from high partial pressure to low partial pressure.


IN LUNGS 

 

• O2 diffuses from alveoli to blood  down its pressure gradient.

 

• CO2 diffuses from blood to alveoli  down its pressure gradient.


TOTAL AND PARTIAL PRESSURES OF GASES


1)Alveolar PO2 = 100 mmHg


2)Pulmonary Artery  PO2 = 40 mmHg

(Pulmonary artery conatins venous blood)


3(Pulmonary Vein PO2 = 100 mmHg

(Pulmonary vein contains arterial blood)



Alveolar-Capillary membrane

(Respiratory membrane)


FACTORS THAT AFFECT GASEOUS DIFFUSION 


1)Partial pressure gradient of the gas across the alveolar- capillary membrane. (60 mmHg for O2 & 6 mmHg for CO2).


2)Surface area of the alveolar-capillary membrane. (about 70  m2).


3)Thickness of the alveolar-capillary membrane. (about 0.5 μ).


4)Diffusion coefficient of the gas that depends on the following parameters :

    •Gas solubility. (CO2 is 24 times soluble than O2).

     •Molecular weight of the gas. (CO2 M.W. is 1.4 times greater than O2).

     •Net effect: CO2 diffusion is 20 times faster than O2


TRANSPORT OF OXYGEN IN BLOOD


•O2 is transported by the blood mainly in two forms:

     -Physically dissolved  in blood = 1.5%

     -Chemically bound  to haemoglobin = 98.5%


PHYSICALLY DISSOLVED OXYGEN 

    

     •Only 1.5 % of total O2 in blood.

     •Dissolved in plasma and water of  RBC. (because solubility of O2 is  very low)

     •It is about 0.3ml of O2 dissolved in  100ml arterial blood (at PO2 100  mmHg).

     •Its amount is directly proportional  to blood PO2.

     •Can not satisfy tissue needs.


CHEMICALLY COMBINED OXYGEN 

    

     •98.5 % of total O2 in blood.

     •Transported in combination with Hb.

     •It is about 19.5 ml of O2 in 100 ml of arterial blood.

    •Can satisfy tissue needs.


OXYGEN COMBINED TO HEMOGLOBIN 


     •Hb is formed of 4 subunits.

     •Each subunit contains a heme group attached to a  polypeptide chain (α or β).

     •O2 binds to the ferrous iron atom in the heme group in a  rapid oxygenation reaction (HbO2).

     •The connection between iron and O2 is weak and reversible.

     •The iron stays in the ferrous state.

     •Thus, each Hb molecule can carry up to 4 O2 molecules.


OXYGEN CONTENT OF BLOOD 


      •It is the total amount of Oxygen carried by blood.

     Which is nothing but the sum of dissolved O2 and O2 combined with Hb ( 0.3 ml/100ml + 19.5 ml/100ml )


Plasma (0.3 ml) + Hb of RBCs (19.5 ml)

= 19.8 ml/100 ml blood.

 

      •It depends mainly on the O2 bound to Hb, as it represents the main component.


OXYGEN CARRYING CAPACITY OF THE BLOOD 

    

     •It is the maximum amount of O2 that can be carried by Hb.

     •Each gram Hb, when fully saturated with O2, can carry 1.34  ml O2.

     •As Hb content = 15 gm/100 ml blood.  So, O2 carrying capacity = 1.34 x 15

= 20.1 ml O2/100 ml blood.

(Hb = 15 gm  Each gm: 1.34 ml O2)

                  

Hb SATURATION WITH OXYGEN 

(%  Hb saturation)


•It is an index for the extent to which Hb can be combined with oxygen.

 

•When all Hb molecules are carrying their maximum O2 load,  Hb is said to be fully saturated (100 % saturated).

 

•PO2 of the blood is the primary factor that determines % Hb saturation.


Importance of Hb saturation


•In arterial blood (High PO2 ):

97% of Hb is saturated with O2


•In venous blood (Low PO2 ):

75% of Hb is saturated with O2

 

•At the lung: high alveolar PO2 (100 mmHg)

Hb automatically loads up (binds) O2.


•At the tissues: low tissue PO2  (40 mmHg)

Hb automatically unloads (releases) O2.


OXYGEN HEMOGLOBIN DISSOCIATION CURVE


•It is a curve that represents the relationship between  blood PO2 (on the horizontal axis) and % of Hb saturation (on the vertical axis) .

Because the % of haemoglobin saturation depends on the PO2 of  the blood.


•It is not linear , it is an S-shaped curve that has 2 parts:

     -upper flat (plateau) part.

     -lower steep part.


In the pulmonary capillaries (lung, PO2 range of 100-60 mmHg).

97% of Hb is saturated with O2.

90% of Hb is saturated with O2 (small change in % Hb

-At PO2 100 mmHg

-At PO2 60 mmHg  saturation).


The upper flat (plateau)  part of the curve


•PHYSIOLOGICAL SIGNIFICANCE


- Drop of arterial PO2 from 100 to 60 mmHg

little decrease in Hb saturation to 90 % which will be sufficient to  meet the body needs.

This provides a good margin of safety against blood PO2

changes in pathological conditions

- Increase arterial PO2 (by breathing pure O2

)little increase in % Hb saturation (only 2.5%) and in total O2 content

of blood.


In the systemic capillaries (tissue, PO2 range of 0-60 mm Hg).

70% of Hb is saturated with O2

- At PO2 40 mmHg (venous blood)  (large change in % Hb saturation).  

The steep or lower part  of the curve

•Physiologic significance:

- In this range, only small drop in tissue PO2

rapid desaturation of Hb to release large amounts of O2

- If arterial PO2 falls below 60 mmHg

Hb occurs very rapidly  tissues.

This is very important at tissue level.


FACTORS AFFECTING O2 HB DISSOCIATION CURVE 


Factors that shift O2-Hb Curve to the right =

decreased affinity of Hb to O2 & increase  O2 release to tissues.


Factors that shift O2-Hb Curve to the left =

increased affinity of Hb to O2 & decrease  O2 release to tissues.


Factors affecting O2-Hb dissociation curve


FACTORS THAT SHIFT O2 Hb CURVE TO RIGHT


•Decreased PO2.

•Increased blood PCO2.

•Increased blood H+ concentration.

•Increased blood  temperature.

•Increased concentration of 2,3 DPG.


FACTORS THAT SHIFT O2 Hb CURVE TO LEFT


•Increased PO2.

•Decreased blood PCO2

•Decreased blood H+

concentration.

•Decreased blood  temperature.

•Decreased concentration of

2,3 DPG


CHANGES IN O2 Hb DISSOCIATION CURVE DURING EXERCISE


There will be:

    •Decreased PO2 in capillaries of active muscles.

     •Increased temperature in active muscles.

     •Increased CO2

     •Decreased pH due to acidic metabolites.

     •Increased 2, 3 DPG in RBCs by anaerobic glycolysis.

All these factors lead to:

      •Shift of O2-Hb dissociation curve to the right.

      •Decrease affinity of Hb to O2.

      •More release of O2 to tissues.


P-50


    •It is the PO2 at which 50% of Hb is saturated with O2.

    •It is an index for Hb affinity to O2.

    •Normally, P50 is 27 mmHg

(At PCO2=40mmHg, pH=7.4, 37°C).


BOHRS EFFECT 


•Represents the effect of PCO2 and H+ (acidity) on the  O2-Hb dissociation curve.

-At tissues: Increased PCO2 & H+ concentration  shift of O2-Hb curve to the right.

-At lungs: Decreased PCO2 & H+ concentration

shift of O2-Hb curve to the left.

So, Bohr's effect facilitates

   i)O2 release from Hb at tissues.

   ii)O2 uptake by Hb at lungs.


Other factors


•CO2: combine reversibly with Hb (at sites other than O2 binding sites)  change in the molecular structure of Hb    decrease in affinity of Hb to  O2.


•H+: combine reversibly with Hb (at sites other than O2 binding sites)

decrease in affinity of Hb to

change in the molecular structure of Hb

O2.


•2,3 DPG:

-Produced by anaerobic glycolysis inside RBCs.

-Binds reversibly with Hb (at β polypeptide chain) decrease Hb affinity to O2.

-Increased by: exercise, at high altitude, thyroid hormone, growth hormone  and androgens.

-Decreased by: acidosis and in stored blood.


O2 DISSOCIATION CURVE OF FETAL Hb


•Fetal Hb (HbF) contains 2 alpha and 2 beta polypeptide chains  and has no  chain which is found in adult Hb (HbA).

 

•So, it cannot combine with 2, 3 DPG that binds only to  chains.

 

•So, fetal Hb has a dissociation curve to the left of that  of adult Hb.

 

•So, its affinity to O2 is high    increased O2 uptake by the fetus from the mother.


O2 DISSOCIATION CURVE OF MYOGLOBIN 


•One molecule of myoglobin has one ferrous atom (Hb has 4  ferrous atoms).

 

•One molecule of myoglobin can combine with only one  molecule of O2 .

 

•The O2–myoglobin curve is rectangular in shape and to the left of the O2-Hb dissociation curve.

 

•So, it gives its O2 to the tissue at very low PO2.

 

•So, it acts as O2 store used in severe muscular exercise when  PO2 becomes very low.


CHLORIDE SHIFT PHENOMENON


•Definition: It is the movement of Cl- in exchange  with HCO-3 across RBC membrane.


•It is responsible for carrying most of the tidal  CO2 in the bicarbonate form.

•It prevents excessive drop of blood pH.


MECHANISM OF CHLORIDE SHIFT PHENOMENON


•Mechanism:


    -CO2  entering the blood diffuses into RBCs    rapidly hydrated to H2CO3 in the presence of the carbonic anhydrase enzyme.

    -H2CO3 dissociates into H+ and HCO-3.

    -H+ is buffered by the reduced (not oxygenated) Hb.

    -HCO-3 concentration in RBCs increases.

    -Some of the HCO-3 diffuses out to the plasma.

    -In order to maintain electrical neutrality, chloride ions (Cl-)  migrate from the plasma into the red cells.


NET EFFECT OF CHLORIDE SHIFT PHENOMENON 


-Increased HCO-3 in both the RBCs and plasma.

-Increased Cl- inside the RBCs.

-Increased osmotic pressure inside RBCs  shift from the plasma.

-Increase RBCs volume increase in the hematocrit  value.

-Buffering of the tidal CO2 with very little change in the  pH.


REVERSE CHLORIDE SHIFT PHENOMENON


•Definition: It is the movement of Cl- in exchange  with HCO-3 across RBC membrane.

•It is responsible for removal of the tidal CO2 by  lungs.


•CARBON DIOXIDE DISSOCIATION CURVE 


•It is a curve which represents the relationship between the total CO2 content and CO2 tension.


•It is linear, in the physiological range of PCO2.


•The normal PCO2 range is:

-40 mmHg in arterial blood with CO2 content of 48 ml/100 ml blood

-46 mmHg in venous blood with CO2 content of 52 ml/100 ml blood.


•This linear relationship means that any change in PCO2 will  produce a great change in CO2 content of the blood.


•Also, at any given CO2 tension, reduced Hb carries more CO2 than  oxyHb.

CO2 dissociation curve


HALDANE EFFECT 


1. Release of O2 in the tissues from HbO2 with formationof deoxygenated haemoglobin stimulates uptake of Co2 by RBC . This is know as Haldane effect

 

2. Co2 dissociation curve various with the partial pressure of O2. As the partial pressure of 02 raises , the Co2 dissociation curve shifts to the right .


CARBON MONOXIDE POISONING


•CO + Hb  forms  carboxyhemoglobin (HbCO).

•CO and O2 compete for the same binding sites on Hb.

•The affinity of Hb for CO is 240 times more than its affinity for  O2.

•CO can interfere with both the combination of O2 with Hb in the lungs and the release of O2 at tissues by:

-Presence of of CO (even in small amounts) binds to a large portion  of Hb preventing its binding to O2.

-CO shifts  O2-Hb  dissociation curve to the left.

 

 APPLIED ASPECTS 


•CYANOSIS :


•This is the bluish discoloration of skin & mucous membranes.

•It is an very important sign in clinicals.

•It denotes the amount of saturation of haemoglobin.

 

•SHORTNESS OF BREATH or SOB or DYSPNOEA :


•Another important sign in clinicals

•Air hunger or consciousness of breathing or laboured breathing.

 •treat the cause or underlying disease

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