O2 and CO2 carriage

Regulation of respiration

P Balasuriya
 O2 transport in blood
O2 is transported in arterial blood
* bound to haemoglobin as oxyhaemoglobin - 97%
Hb is only oxygenated, not oxidised (iron remains in
the ferrous form )
* dissolved in plasma - 3% (solubility of O2 is poor)

At tissue level, O2 enters the interstitial fluid from blood in

capillaries and diffuses into cells.
After giving up O2 and gaining CO2 venous blood returns to
heart.
Oxygen dissociation curve shows the relationship
between partial pressure of O2 (PaO2) in the blood and
the percentage saturation of Hb with O2
Combination of O2 with the first heme group in the Hb
molecule increases the affinity stepwise for each
successive groups
Therefore the curve is not linear but has a sigmoid shape
The saturation does not become significantly reduced
with decrease of PaO2 until it reaches about 65 mm Hg
50% saturation (P50) occurs at a PaO2 of 30 mm Hg
 Oxygen dissociation curve

O 2saturation %

P50

PaO2 (mm Hg)

At rest, the oxygen dissociation curve operates between PaO2
95 mm Hg (arterial) and 40 mm Hg (venous)
It shifts to the right when there is a:
* rise in temperature
* fall in pH
* increased PCO2
* increase in red cell 2-3 BPG (combines with β chains of Hb)
This allows more O2 to be freed from Hb at a higher PaO2
Exercise produces these effects
It shifts to the left in the opposite conditions
Shift of O2 dissociation curve
Bohr effect:
Increase in CO2 and H+ at tissue level reduces the pH
with a decrease in O2 affinity of Hb and reducing O2
saturation .
Shift of the curve to the right has a significant effect
by releasing O2 to tissues
Decrease in O2 affinity of Hb when pH of blood falls
is called the Bohr effect
The reverse occurs in the alveoli when CO2 diffuses
out thus increasing O2 saturation
Double Bohr effect occurs in the placenta
1g of Hb when fully saturated can carry 1.34 ml of O2

If the Hb concentration is 15g.dL-1, O2 capacity is 20 ml.dL-1

Hb is only 97% saturated in arterial blood

Therefore, the O2 content is only 19.4 ml.dL-1

 CO2 transport in blood

CO2 from cells diffuses into blood and is transported to

the lungs
* mostly as HCO3- formed mainly in red cells
(70%) by its reaction with water (catalysed by
enzyme- carbonic anhydrase) and partly in plasma
* dissolved in plasma (7%)
* bound to haemoglobin in the red cells to form
carbamino-haemoglobin (23%)
As HCO3- :

CO2 diffuses into RBC and reacts with water catalysed by

carbonic anhydrase

CO2 + H2O H2CO3 H+ + HCO3-

70% of HCO3- formed diffuses into plasma in exchange for

Cl- by means of a carrier protein.
This is called chloride shift in venous blood.

The reaction of CO2 with water also occurs to a smaller

extent in plasma
H+ formed by the reaction is buffered by Hb.
Reduced Hb (deoxyHb) in venous blood is a better buffer
than oxyHb

This effect of deoxyHb enabling venous blood to carry

more CO2 is called the Haldane effect
CO2 transport in blood
In the lungs when Hb gets oxygenated, H+ is released
and combines with HCO3- releasing CO2. More HCO3-
enters the RBC and Cl- diffuses back into plasma.

As RBC in venous blood has extra ions (HCO3- or Cl-)

they absorb water and are larger than RBC in arterial
blood

Inspite of buffering, venous blood has a lower pH than

arterial blood
Regulation of respiration
Respiration is an involuntary function, but can be
influenced voluntarily
Respiratory muscles are skeletal muscles, but are mostly
under involuntary control from the respiratory center.
Involuntary control is more powerful.
 Respiratory center
Respiration is regulated by the respiratory center (RC)
in the medulla.

The dorsal respiratory group of neurons (DRG) is the

inspiratory part. It sends impulses to the motor nuclei of
inspiratory muscles in the spinal cord, to cause inspiration

The ventral respiratory group (VRG) is the expiratory

part. It is quiet during quiet breathing and expiration is a
passive process
The activity of the DRG is rhythmic, gradually building
up during inspiration and ending abruptly (ramp signal)

The DRG sends impulses to the motor nuclei (in the

spinal cord) of nerves supplying inspiratory muscles, to
cause inspiration

The expiratory part only discharges during forced

breathing
 Control by pontine centers
The rhythmic discharge of neurons in the RC is
modified by groups of neurons in the pons
Pneumotaxic center (PC)
Controls the duration and the rate of inspiration
Apneustic center
Leads to prolonged inspiration (opposed by the PC)
 Control by vagus
Stretching of the lungs during inspiration causes
stimulation of stretch receptors
Afferent impulses along the vagal fibers inhibit the
inspiratory discharge
Acts together with the PC to keep the apneustic center
in check
Pons

Medulla
 Regulation of breathing
Respiration has to be regulated to maintain the partial
pressures of O2 and CO2 in arterial blood within
narrow limits in spite of changes in external or internal
environments
The rate and depth of respiration change appropriately
without any voluntary effort
Regulation is done according to information received
from receptors (mainly chemoreceptors) and from
higher centers
 Chemoreceptors
1. Peripheral chemoreceptors are present in carotid
bodies at the bifurcation of the common carotid
arteries and in aortic bodies in the aortic arch
Nerve supply: carotid bodies - branches of the IX
aortic bodies - branches of the X

They are stimulated by chemical changes in arterial

blood
* increased PaCO2
* decreased PaO2 (hypoxia)
* decreased pH
 Control of the RC by peripheral chemoreceptors

RC
Responses to decreased PaO2
Hypoxia stimulates the RC through the chemoreceptors
and causes hyperventilation.
The effect is more marked when the PaO2 is < 60mm Hg
This helps to increase the PaO2

Responses to increased PaCO2

Increase in PaCO2 leads to hyperventilation and blowing
out of CO2 correcting the defect
Decrease in PaCO2 has the opposite effect
Responses to changes in pH
When the pH of blood decreases, RC is stimulated and
hyperventilation blows out CO2 producing a fall in the H+
concentration
H+ + HCO3- H2CO3 H2O + CO2
When the pH of blood increases, RC is depressed and
retains CO2
The reaction proceeds in the opposite direction and
corrects the alkalosis
A change in pH is corrected within seconds
2. Central chemoreceptors are present in the medulla
and they are stimulated by increased PaCO2
CO2 diffuses into brain interstitial fluid and decreases pH

H2O + CO2 H2CO3 H+ + HCO3-

* Chemoreceptors 1 and 2 when stimulated send

impulses to the RC to increase respiration and vice
versa
 Control of RC from higher centers

Emotions e.g. excitement, arising from higher

centers stimulate the RC
 Regulation of RC activity

Hypothalamus  (emotions, pain)

RC

Chemoreceptors + Receptors in lung -

central
peripheral
 Voluntary control of breathing

Voluntary system is located in the motor cortex

and sends impulses to the respiratory motor
neurons supplying:
* the diaphragm (phrenic nerve C3-5 )
* intercostal muscles (T1- 12)

Voluntary breathing or breath-holding is possible

only for a limited time as involuntary control is
more powerful

Voluntary control facilitates talking, singing, etc

Respiration during sleep

Activity of the reticular activating system (RAS) in the

brain stem is associated with the awake state
When active, stimulates respiratory drive

A decrease in ventilation occurs during sleep due to :

• reduced activity of RAS
• reduced sensitivity of the RC to PCO2

Brief periods of apnoea (<10s) can occur in normal

sleeping adults
Ventilation/ PCO2 curve

Curve shifts to the right

* during sleep
* drugs e.g. sedatives,
narcotics, opiates, etc
Ventilation decreases for a
given PCO2
Airway resistance

Resistance is mainly in the medium sized airways

Lower during inspiration because small airways get

stretched

In disease conditions, smaller bronchioles play a part,

because they are easily occluded by muscle
contraction, oedema and mucus
 Lung compliance

Pulmonary compliance is the ability of the lungs to stretch

(change in volume relative to a change in pressure)

Compliance = change in volume/ change in pressure

0.1L.cm.H2O-1

Compliance is greatest at moderate lung volumes, and much

lower at very low or very high volumes

Pulmonary surfactant reduces surface tension, increasing

compliance and preventing collapse at the end of expiration.