RESPIRATORY PHYSIOLOGY

• WORK OF BREATHING
– AIR WAY RESISTANCE
– COLLAPSING TENDENCIES/ELASTIC RESISTANCE
– SURFACE TENSION AND SURFACTANT
• LUNG VOLUMES AND CAPACITIES
• TRANSPORT OF GASES
 Work of breathing
• Work is performed by respiratory muscles during respiration
• During quite breathing, the body spend 3-5% of its total
energy expenditure on respiration
• In heavy exercise, may increase up to 50%
• The expended energy is spent as follows:
– moving inelastic tissues (viscous resistance)—7%
– moving air through the respiratory passages—28%
– Moving elastic tissues of the chest wall and lungs (compliance
work)—65%
 Tissue resistance work
• This is the energy spent in overcoming resistance of
the in-elastic tissues of both the lung and thorax
• It is also known as viscous resistance
• It constitutes about 7% of total work of breathing
 Airway resistance work
• Work required to move air along the airways
• It is roughly 28% of total
• 50% is due to extra-thoracic airway resistance
NOSE is a major contributor
• Is made variable due to flaring.
• Each nostril alternates between high and low
resistance every 90 minutes (changed by congestion
& secretions).
 Upper airway resistance
• Pharyngeal
– major point of resistance is at glottis.
– Determined by facial bones, lympohoid tissue, fat deposition (obesity)
• Larynx
– 30% of total airway resistance-------consider laryngospasm
– Is varied by abductors of vocal cord at the beginning of inspiration
– Adductors function in RDS to maintain lung volumes hence the
expiratory grunting (FRC is low in RDS)
 Lower airways resistance
• Major site of resistance is medium sized bronchi up
to the 7th generation.
• Very small bronchioles contribute little to resistance,
– Although they have a very small diameter, but there are
so much of these small airways hence counteracts this.
– This is why small airways disease must be fairly advanced
before clinically detectable
Factors affecting airways resistance
• Age
– older people have more fat around pharnyx = higher resistance
• Gender
– women have smaller airways than men, hence have higher
airway resistance
• Position
– standing better than lying
• Method of breathing
– oral breathing offers less resistance than nasal
 Factors affecting airways resistance
• Density of inspired gas
– density  resistance (increased pressure increases
gas density)
• hence, Heliox (reduces airway resistance 3x) is used in
severe airway flow limitation.
• Viscosity of inspired gas
– gas viscosity – reduces resistance gas e.g. by
breathing a helium-oxygen mixture.
 Factors affecting airways resistance
• Air flow pattern
– laminar/turbulent flow – turbulent flow increases resistance.
• RR = velocity = more turbulent flow = higher resistance
• Lung volume
– Lung volume = Airway resistance
–  lung volume = Airway resistance .
• At low lung volumes small airways tend to close.
Factors affecting airways resistance
• Tone of bronchial smooth muscle
– Bronchoconstriction narrows the airways &  resistance.
– Bronchodilation widens the airways & resistance
• Obstruction
– Mucous plug, secretions, foreign body, etc
• External Factors
– External compression by tumour, haematoma,
pneumothorax
 Compliance work
• Energy required to expand lungs and thorax against
the elastic force
• It is approximately 65% of the total work.
• 1/3 (22% of total) of compliance work is used to
stretch the elastic tissues of lungs & chest wall
• 2/3 (43% of total) of the compliant work is used to
overcome surface tension
 Collapsing tendency of the lungs

• The lung has a tendency to collapse due to:

– Intrinsic elasticity.
– Alveolar surface tension
• Factors preventing Collapsing tendency of lungs
– Intra-pleural or intrathoracic pressure
– Pulmonary Surfactant
– Alveolar interdependence : All alveoli are surrounded by others
& if one area collapses large expanding forces will develop on
them because the surrounding parenchyma is expanded
 Intrinsic elasticity of the lungs
• This is mainly due to elastin and collagen fibres
interwoven among lung parenchyma.
• In deflated lungs, these fibres are elastically
contracted and kinked
• when the lungs expand, the fibres become
stretched and elongated, but still exerting elastic
force to return to the natural state.
 Elastance and Compliance
• While the elastic properties of the lung are important
to bring about expiration, they also oppose lung
inflation.
• This resistance to inflation is termed elastance.
However, compliance is the preferred term to
describe the elastic properties of the lung.
• Compliance (a reciprocal of elastance), is a measure
of the ease with which the lungs are inflated.
 Compliance
• Compliance is measured as the change in volume
for a given change in pressure dV/dP
• Thus, a structure with high elastance has a low
compliance.
• The compliance of the lungs is 0.2 L/cm of water
• The compliance of the thorax is also equal to 0.2
L/cm of water.
 compliance
• But the compliance of the lungs and thoracic cage
together is equal to 0.1 L/cm of water.
• This is so because the lungs try to pull thoracic cage
inwards while the thoracic cage tries to pull lungs
outwards.
• Therefore, it is more difficult to distend the lungs and
thoracic cage together than either of them individually.
 compliance
• Compliance decreases as the lung becomes fully
distended and cannot stretch further, because the
lung has reached its elastic limits, set by the
biomechanical properties of cartilage in conducting
airways and a network of connective tissues in the
alveolar walls.
• Absolute compliance depend on body size because
– lung volume changes with size, but pressures do not.
 Specific compliance
• Therefore, the compliance of persons in whom one lung is
removed or children in whom lung volumes are small, will be
below normal
• Specific compliance is defined as compliance per liter of a lung
volume. It is expressed as a fraction of the functional residual
capacity (FRC)
– {Specific compliance = compliance / FRC}
• Since FRC is proportionately lower in children, specific compliance
will essentially remain constant irrespective of age.
 low compliance
Causes of low compliance of lungs.
– i. Surface tension
– ii. Edema of lungs
– iii. Fibrosis
– iv. Block in bronchial tubes.
Causes of low compliance of lungs and thorax together.
– i. Kyphosis
– ii. Scoliosis
– iii. Fibrotic pleurisy
– iv. Fibrotic muscles
 Alveolar surface tension and surfactant
• Alveolar surface tension is the tension exerted on the surface
of alveolar membrane by the fluid secreted from alveolar
epithelium which tends to collapse them.

• Pulmonary Surfactant(surf=surface, act=active, ant=agent)

• is a phospholipid secreted by
– Type II alveolar cells
– Clara cells
 Surfactant- Synthesis and Secretion
• Organelles containing whorls of phospholipids are formed in
these cells.
• These organelles are 100-A˚ thick stacks called lamellar bodies.
• They are transformed into tubular myelin (which forms the
phospholipid film) during secretion into the alveolar lumen by
exocytosis.
• Following secretion, the phospholipids line up in the alveoli
with their hydrophobic fatty acid tails facing the alveolar lumen.
 Surfactant-Secretion and Composition
• Formation of the phospholipid film is greatly facilitated by
proteins in the surfactant [surfactant protein (SP)-A, SP-B,
SP-C, and SP-D]
– SPA is a large hydrophilic glycoprotein. Its functions includes
regulation of the feedback uptake of surfactant by the type II
alveolar epithelial cells.
– SP-B and SP-C are smaller hydrophobic proteins, which facilitate
formation of the monomolecular film of phospholipid on at
upper surface of the surfactant.
– SP-D and SP-A are involved in, opsonization, antioxidant and
anti-inflammatory functions.
 Surfactant- Composition
LIPIDS==============90%
• Phospholipids--------------------77%
– **Dipalmitoylphosphatidylcholine-----62%
– Phosphatidylglycerol--------------------5%
– Other phospholipids--------------------10%
• Neutral lipids---------------------13%
PROTEINS==========8%
CARBOHYDRATE====2%
**DPPC is the most important component.
 Surfactant-Turnover

• There is rapid synthesis and turnover of surfactant

• The half-life is approximately 14 hours
• Some of the protein– lipid complexes in surfactant are taken
up by the type II alveolar cells through endocytosis and
recycled
• It is also removed from the alveoli by macrophages
• If blood flow is abolished (e.g. by PE or bye pass surgery), then
surfactant can be depleted rapidly
 Surfactant-Actions
• It opposes the normal attractive forces between
the molecules of the liquid surface.
– It reduces surface tension at smaller areas or when the
alveoli move closer together during expiration, because
the molecules of DPPC are crowded closer together &
therefore repel each other more.
– It however, moves further apart as the alveoli enlarge
during inspiration, therefore, increasing surface
tension.
 Functions of surfactant
• Lowering of surface tension by surfactant improves
compliance of the lungs. This reduces the muscular
effort required for breathing.
• Prevents emptying of small alveoli into large alveoli.
Hence, surfactant contributes to stability of alveoli.
– The law of Laplace predicts instability between alveoli of
different radii (r) with small alveoli tending to empty into
larger ones (P=4T/r)
 Functions of surfactant
• Prevent the lung from collapsing during
expiration
• Prevent pulmonary oedema: Surface forces
tending to collapse the alveoli will lower
interstitial pressure around capillaries in the
alveolar walls, and tend to draw fluid out of
capillaries.
 IRDS, ARDS AND SIGHS
• Respiratory distress syndrome:
– lessthan 28 weeks old (60%), 28-34 weeks old (30%), 35-37
weeks (5%) and in Full term neonates (1%),
• Low quality and quantity of surfactant (surfactant is higher
in new born)
– ARDS, laboured breathing, acidosis, tarchypnea and increase in
dead space air.
– ARDS, atelectasis, pulmonary oedema, hypoxemia, Hyperoxia
(O2 toxicity to lungs), lung damage, coagulam of cellular debris
and plasma proteins (hyaline membrane) lining the alveoli
 LUNG VOLUMES

• Tidal Volume (VT): volume of gas inspired or expired

during a normal spontaneous breath.
• Inspiratory Reserve Volume (IRV): volume of gas that
can be inspired at the end of a spontaneous inspiration.
• Expiratory Reserve Volume (ERV): volume of gas that
can be expired at the end of a spontaneous Expiration.
• Residual Volume (RV): volume of air in lungs that cannot
be forcefully expired or the volume of air in lung at end
of a vital capacity.
 LUNG CAPACITIES
• Inspiratory Capacity (IC): the maximal volume of air that
can be inspired from normal end-expiration or VT + IRV
• Vital Capacity (VC): maximum volume of gas that can be
expired after a maximal inspiration or IRV + VT + ERV
• Functional Residual Capacity (FRC): total volume of air in
the lung at end of normal end-expiration or ERV + RV.
• Total Lung Capacity (TLC): total volume of gas in lung at
maximal end inspiration or VC + RV or IRV + VT + ERV +
RV.
 LUNG VOLUMES AND CAPACITIES

• LUNG VOLUMES
– Tidal vol. (500ml)
– Inspiratory reserve vol. (3000ml)
– Expiratory reserve vol. (1100ml)
– Residual vol. (1200ml)
• LUNG CAPACITIES
– Inspiratory cap. (3500ml)
– Functional residual cap. (2300ml)
– Vital cap. (4600ml)
– Total lung cap. (5800ml)
 Physiological variations in vital capacity

• Sex: VC is less in females.

• Body built: VC is slightly more in heavy built persons.
• Posture: VC is more in standing position & less in lying position.
• Athletes: VC is more in athletes.
• Age:
– Dead space and residual volume increases
– VC and maximum minute ventilation decreases
– Ability to remove mucus from respiratory passageways decreases
– Gas exchange across respiratory membrane is reduced
 DIFFUSION ACROSS THE RESPIRATORY MEMBRANE

• The air in the alveoli comes to equilibrium with the blood

oxygen and carbon dioxide, because, the respiratory
membrane is so efficient
– Large surface area, 70m2
– Shorter diffusion distance, 0.5 um
– High diffusisbility, Lipid membrane.
 DIFFUSION ACROSS THE RESPIRATORY MEMBRANE

• During normal, quiet breathing, the diffusing capacity of

oxygen is about 230 milliliters/minute (25mls/mmhg/minute)
• Blood takes about 1sec to travel across a pulmonary capillary
However, blood in pulmonary capillaries become fully
saturated in the first 1/3 of the capillaries
• O2 is 95% equilibrated after 0.2sec and fully equilibrated after
0.25- 0.3sec while, Co2 equilibrates fully in 0.015sec
• At rest, 98% of blood become saturated
(PO2=104mmHg) with O2 and the rest (2%) is shunted
through the bronchial circulation
• Hence, pulmonary vein O2 saturation is 95mmHg.
• If arterial blood were to contain only dissolved O2, then
cardiac output would have to be 100 L/min to deliver
enough O2 to the tissues for a normal metabolic
rate(230mls)
 TRANSPORT OF RESPIRATORY GASSES (OXYGEN)

• Because the physical solubility of O2 in blood is 0.003

mL/dL /mm Hg at 37C and the maximal arterial PO2 (PaO2) is
100 mm Hg hence, only 0.3 mL/dL would be physically
dissolved in the plasma .
• Hemoglobin serve to increase O2 concentration in blood so
that a cardiac output of only 5 L/min is sufficient for the
resting metabolic demands of the body.
• 97% of O2 in blood is transported by combining with
hemoglobin and only 3% is dissolved.
 Structure of Haemoglobin
• Succinyl-CoA binds with glycine to form a pyrrole molecule.
• Four pyrroles combine to form protoporphyrin IX,
• This then combines with iron to form a heme molecule.
• Each haem molecule combines with a long polypeptide
chain of globin to form a subunit of hemoglobin called a
hemoglobin chain
• Four of these chains bind together loosely to form the
hemoglobin molecule.
 Structure of Haemoglobin
• Each of the four iron atoms can combine loosely
and reversibly with one molecule of oxygen making
a total of four molecules (eight atomic oxygen).
• The iron is in ferrous (Fe2+) form and do not get
oxidized upon combination with oxygen
• If the ferrous ion is oxidised to its ferric form it
becomes methaemoglobin which cannot carry O2.
 STEPS IN HAEMOGLOBIN SATURATION (OXYGEN LOADING)

• PO2 of RBC fluids is the same as in the plasma.

– Oxygen diffuses from the alveoli into the plasma due to the
PO2 gradient, this raises plasma PO2.
– Now there is a gradient between PO2 of plasma and PO2 of
RBC fluids.
– Oxygen now diffuses from plasma to RBC fluid.
– As soon as oxygen enters the RBC it combines with
hemoglobin.
• Hemoglobin mops up oxygen and does not allow PO2 of RBC fluid to rise.
– The process continues till hemoglobin cannot pick up any
more oxygen.
 OXYGEN LOADING
• Then the PO2 of RBC fluids rises, to equal that in the plasma
and diffusion from plasma to RBC stops.
• The PO2 of plasma also rises to equal that in the alveoli, and
diffusion from alveoli to the plasma therefore stops.
– This entire process takes only 0.25-0.3 seconds
• Each gram of pure Hb can combine with 1.39mL of O2 when
all the available binding sites are occupied.
• Due to impurities such as methaemoglobin, it could only
carry 1.34ml O2 at 100% saturation,
– so 1.34 X 15gm = 20.1ml O2 in 100% saturation.
 OXYGEN OFF-LOADING
• In deoxyhemoglobin, the globin units are tightly bound in a
tense (T) configuration
– this reduces its affinity for O2.
• When O2 is first bound, the bonds holding the globin units
are released, producing a relaxed (R) configuration
– this exposes more O2 binding sites.
– The net result is a 500-fold increase in O2 affinity
• In tissues, these reactions are reversed, releasing O2.
– The transition from one state to another occur about 10x/sec
(100 million times in the life time of an Rbc)
 OXYGEN OFF-LOADING
• In tissue capillaries, where PO2 is low
(40mmHg), Hb releases O2 such that in the
veins, it becomes 75% saturated (40 mmHg
of PO2) containing 14.4 mls O2/dl of blood
• Sometimes, the PO2 falls to as low as 15
mmHg hence the Hb carrying only
4.4milliliters of oxygen/dl
 OXYGEN OFF-LOADING

• The intra-cellular PO2 is 25mmHg,

hence, O2 diffuses from the interstitial
fluid into the cells.
• Whenever the intracellular PO2 is above
1 mm Hg, the rate of oxygen usage by
the mitochondria becomes constant for
any given concentration of ADP
Oxygen association-dissociation curve of Hb
• The oxygen–hemoglobin association-
dissociation curve relates percentage
saturation of the O2 carrying power of
hemoglobin to the PO2.
• It has a characteristic sigmoid shape
due to the T–R interconversion.
 Oxygen association-dissociation curve of Hb

• The upper portion of the curve, between a PO2 of 70 to

100 mmHg, is nearly flat.
– This portion of the curve is often referred to as the association
part of the curve
• It is important in the loading of O2 (association of O2 with Hb) in
the lung capillary.
• It ensures oxygenation of most of the Hb even when alveolar PO2
is decreased due to altitude ascension or pulmonary disease
 Oxygen association-dissociation curve of Hb
• The steep sloping part of the curve, between PO2 of 20 to
50mmHg is termed the dissociation portion of the curve.
– It is important in the tissue capillaries where a large
amount of O2 can be unloaded for a relatively small
change in PO2.
• The P50 is used to specify the position of the curve
• It is on the steepest part of the curve & is therefore the most
sensitive point for change of position.
• it is an index of O2 affinity to Hb hence .
– a useful point for specifying the position of the curve
 Oxygen association-dissociation curve of Hb

• P50 for adult Hb is 26.6mmHg.,

• A decrease in P50 is referred to as a left shift
and indicates an increased Hb-O2 affinity
• Similarly, increased P50 is referred to as a
right shift and it reflects a decrease in Hb-O2
affinity.
 Advantages of the sigmoid curve

• If PO2 in alveolar gas falls, O2 loading will be minimally

affected b/cos:
– At the plat top, large partial pressure between alveolar gas & blood
continues to exist when most of the O2 has been transferred, this
hastens diffusion.
• The steep lower part means the peripheral tissues can
withdraw large amounts of O2 for only a small drop in
capillary PO2. This assists with oxygen diffusion into the cells.
Factors that affect the sigma curve
 Shifts in the oxy-Hb dissociation
• Shift in the curve due to changes in the blood PCO2 or
pH are termed the Bohr effect
• Bohr Effect
• It is the effect by which the presence of CO2 decreases
the affinity of Hb for O2.
– i.e, shifts the O2-dissociation curve to the right
• In the tissues, due to metabolic activities, pCO2 is high
& pO2 is low.
– Due to pressure gradient, CO2 enters the blood and O2 is
released from the blood to tissues.
 Effects of 2,3-DPG
• RBCs anaerobically catabolyze glucose to lactic acid via the
glycolytic pathway because they do not contain mitochondria.
• Since RBCs do not store glycogen, they must constantly
catabolyze glucose from the bloodstream via this pathway and
the hexose monophosphate shunt as a source of energy.
• The glycolytic pathway serves three functions in the RBC
– ATP production
– 2,3 DPG production
– NADH production.
 Production of 2,3 DPG in the RBC
• In most cells, 2,3 DPG is a trace constituent, but in the RBC, it
accounts for about two thirds of the total cell phosphorus.
• The precursor for 2,3 DPG is 1,3 DPG
– In most cells 1,3 DPG is quickly converted to 3
phosphoglycerate + ATP.
• But in Rbcs, the enzyme DGP synthase shunts 1,3 DPG to 2,3
DPG, (which is later converted to 3 phosphoglycerate) this is
known as Rapoport-Luebering shunt
 Effects of 2,3-DPG
• The rate of 2,3 DPG production is controlled by
the rate of glycolysis.
• During periods of low oxygen, the RBC employs
the Rapoport-Luebering shunt.
• While ATP formation is lost in this conversion, the
2,3-DPG formed attaches to the globulin chain of
Hb and converts the Hb from a relaxed to a tense
state hence reduces its affinity for O2.
 Effects of 2,3-DPG
• 1 mole of deoxyhaemoglobin binds 1 mole of 2,3-DPG
– HbO2 + 2,3-DPG ↔ Hb- 2,3-DPG + O2
• An increase in 2,3-DPG shifts the above equilibrium to the
right, causing more O2 to be liberated.
– This improves tissues ability to extract more oxygen from each gram
of haemoglobin.
• This does not impair oxygen uptake in the lungs much due to
the flat upper part of the ODC.
– Instead, the P50 is raised.
• T½ for 2,3 DPG = 6 hours
 Factors affecting 2,3-DPG concentration

Increased 2,3-DPG - anaemia, alkalosis,

hypoxaemia, altitude, exercise, pregnancy,
hyperthyroidism & hyperphosphataemia
Decreased 2,3-DPG - acidosis,
hypophosphataemia, hypothyroidism &
hypopituitarism
 2,3 DPG in stored blood
• 2,3 DPG may deplete in stored blood, which shifts the
ODC to the left & impairs oxygen uptake by tissues.
– Acid environments increase the rate of loss of 2,3 DPG
(acid-citrate-dextrose)-- its low pH results in high 2,3 DPG
loss.
– CPDA (citrate-phosphate-dextrose-adenine) solution is the
most ideal preservative because depletion of 2,3 DPG
occurs less due to its higher PH. It also contains adenine
and phosphate for ATP generation.
 Transport of CO2
• Carbon dioxide is continually formed by metabolic
processes.
• It diffuses from its site of production (mitochondria) into
interstitial fluid, then to blood down its concentration
gradient.
• Arterial blood contains 48mL CO2 /100mL blood & mixed
venous blood contains 52ml CO2 /100mL blood.
– Hence, 4ml of CO2 per dL of blood is added in tissues
– Therefore, about 200ml of CO2 is produced per minute
 Production of CO2 in the body
• CO2 is a by-product of aerobic metabolism
– Glycosis + TCA
• Pyruvic Acid + Coenzyme A = Acetyl CoA + 2CO2 + 4H
• 2Acetyl CoA + 6H20 + 2ADP = 4CO2 + 16H +2CoA + 2ATP
– Pentose Phosphate Pathway
• Glucose + 12NADP+ + 6H20 = 6CO2 + 12H + 12NADPH
• Its production is affected by Respiratory quotient of substrates:
– RQ is the ratio in the steady state of the volume of CO2 produced to O2
consumed per unit time. RQ for CHO = 1.0. RQ for fat = 0.7. Average in the
body = 0.82
• Other factors include: metabolic rate, Height, weight, Sex, age
 Transport of CO2

• CO2 is transported in blood in 4 ways:

– As carbonic acid (negligible)
– As dissolved form (7%)
– As carbamino compounds (23%)
– As bicarbonates (70%)
 Transport of CO2
Transport of CO2 as carbonic acid
• Some CO2 combines with water in the plasma to form carbonic acid.
– This rxn is very slow due to the absence of carbonic anhydrase enzyme in
the plasma.
– Hence CO2 transport in this form is negligible
Transport of co2 in the dissolved form
• This obeys Henry’s law
– CO2 is x20 more soluble than O2.
– Therefore this accounts for a much greater proportion than dissolved O2.
– It transports about 3mls/dl of blood
– This is about 7% of total CO2 carriage
 Transport of CO2
Transport of CO2 as bicarbonate (70%)
• From plasma, CO2 enters the RBCs due to conc. Gradient
• In RBCs: CO2 combines with water to form carbonic acid
– this rxn is accelerated by Carbonic anhydrase enzyme richly found in
the RBCs
– CA accelerates the reaction rate about 5,000 folds
• Carbonic acid is unstable & rapidly dissociates into HCO3- and
H+.
• This increases the HCO3- conc. in the RBCs.
• There is also a build up of H+ in the RBCs
 Transport of CO2 as bicarbonate (70%)

• The H+ combine with Hb because Hb protein is a powerful acid-base

buffer
– Buffering of H+ by haemoglobin permits more CO2 to be carried as bicarbonate
than if there were no Hb present.
• most of the H+ ions bind to deoxy Hb
– This is because deoxy Hb is less acidic & therefore, a better proton acceptor,
than the oxygenated form.
• In essence, reduced Hb in the peripheral blood helps loading of CO2
whereas oxygenation that occurs in the pulmonary capillaries assists in
unloading of CO2
 Transport of CO2 as bicarbonate (70%)
• The HCO3- diffuses thru the cell membrane (Hamburger effect) into
the plasma in exchange for Cl- (Chloride Shift)
• Chloride Shift or Hamburger Phenomenon
– It is the exchange of a chloride ion for a bicarbonate ion across the
erythrocyte membrane.
– NaCl is present In a dissociated form in the plasma (Na+ and Cl-)
– When the –ve charged HCO3- ions move out of the RBCs into the plasma, the
–ve charged Cl- ions move into the RBCs to maintain electrochemical balance
– The HCO3- ions combine with Na+ ions in the plasma to form sodium
bicarbonate (NaHCO3-)
– In this form, the CO2 is transported in the blood.
 Water shift
• When tidal CO2 is released by the tissues, it enters
the RBCs & is converted to HCO3-.
• The HCO3- attracts water by osmosis causing water
shift.
– Due to this, the RBCs in the venous blood are more
swollen
• Hence, Hematocrit in the venous side is higher than in the
arterial side
– because the RBCs in the venous side are larger than on the arterial side
 Transport of CO2 as carbamino compounds (23%)
• Combination of CO2 with terminal amine groups in blood proteins
(Hb & plasma proteins) to give the carbamino compounds
(carbamino proteins and carbaminoHb)
• Hb is quantitatively more important than plasma proteins because
– It is present in higher concentrations 15g/dl vs. 7g/dl
– Has more histidine residues than plasma proteins.
– It is a tetramer with 4 N-terminals whereas albumin has only
one.
– Formation of carbamino compounds increases as Hb is
deoxygenated.
 Haldane effect

• Haldane effect is where oxygenation displaces CO2 from

Hb (it is opposite to Bohr effect)
– Due to the combination with O2 in the lungs, Hb
becomes strongly acidic.
• The highly acidic Hb releases H+ ions which
combine with HCO3- to form carbonic acid.
• Carbonic acid dissociates into CO2 & hence CO2 is
displaced from blood.
 Reverse Chloride Shift
• It helps in elimination of CO2 from the blood when blood
reaches the lungs & flows thru pulmonary capillaries.
• When the blood reaches the alveoli, NaHCO3-dissociates
into Na+ & HCO3 ion which moves into the RBCs in
exchange for Cl- .
• At the same time, O2 also enters the RBC and displaces
the H+ ion from the Hb which combines with HCO3- ion &
forms carbonic acid.
• The carbonic acid dissociates into CO2 & H20 and CO2 is
expelled.
 Differences in the respiratory system of the neonate & adult

• Epiglottis - U shaped
• Larynx – Position: opposite C3/C4 neonates, C5 @ 3yrs, C6 = adult
position @ 6yrs
• Narrowest part: Cricoid ring, after puberty = vocal cords
• Trachea – length varies from 3.2-7cm depending on the baby’s size
• Tongue - large
• Mandible – angle of the mandible = 140 neonates & 120 adult
• Shape of chest – ribs are more horizontal (limits anteroposterior
expansion), lack of buckle handle mechanism (limits transverse
expansion)
• Muscle fibre type - type 1 fibres for sustained contraction in diaphragm
+ intercostals  respiratory fatigue. %type 1 preterm, neonate, full
maturity: diaphragm 10, 25 + 55%, intercostals 20, 45 + 65%
 Differences in the respiratory system of the neonate & adult

• RR – newborn 30-40 falling to 15 in late childhood. The high rate allows

minimal work of breathing to overcome compliance of the respiratory
system.
• Respirations are irregular + mainly diaphragmatic
• Obligate nasal breathers – mouth breathing is difficult due to the
cephalad larynx & large tongue
• Minute ventilation – 220ml/kg (twice adults)
• FRC – 40% of TLC. Outward recoil of the chest wall is very low
(cartilaginous rib cage + poorly developed respiratory muscles). Inward
recoil of lung is slightly lower than adults. during GA the FRC decreases
to very low values due to decreased intercostal muscle tone.
• Small airway closure occurs because the elastic recoil of the lungs is low
 closing capacity > FRC. Closing capacity as a percentage of TLC is high.
 Neonatal respiratory physiology
• O2 reserve – coupled with higher O2 consumption leads to rapid hypoxaemia.
• Compliance – increases in the first few hours of birth from 1.5-6ml/cmH2O.
Specific compliance is similar in neonates, infants + adults. Due to the very
compliant cartilaginous rib cage airway obstruction  sternal retraction
• Airway resistance – decreases from 90cmH2O/L/sec in first minute to
25cmH2O/L/min at end of day 1. The nasal passages contribute 50% of total
airway resistance.
• Ventilation perfusion mismatch = 0.4 which is significant due to small airway
closure  low normal PaO2 = 50-70mmHg. This hypoxaemia causes a sustained
increased ventilation by day 10.
• Chemoreceptors: CO2 – the CO2 response curve is left shifted ventilatory
increases occur at lower CO2 tensions.
• Apneoas – apnoeic spells (due to Hering-Breuer reflex) lasting 5-6sec normally
occurs 5-6 times per hour. This decreases at 15-24 weeks. Those lasting >15sec
with bradycardia + cyanosis are significant.
 REGULATION OF RESPIRATION
The process of respiration is regulated by two mechanisms:
• Nervous mechanism
• Chemical mechanism
• Nervous Mechanism
– It includes the respiratory centers, afferent and efferent nerves.
• Respiratory centers
– They are a group of neurons that control the rate, rhythm & force of respiration. These centers
are bilaterally situated in the reticular formation of the brain stem.
Respiratory centers are classified into two groups:
• Medullary centers which are made up of:
– Dorsal respiratory group of neurons
– Ventral respiratory group of neurons
• Pontine centers which are:
– Pneumotaxic center
– Apneustic center
• Medullary respiratory centers control each other:
– During inspiration:
• DRG neurons inhibit the expiratory neurons of VRG
– During expiration:
• Expiratory neurons of VRG inhibit the DRG.
• Dorsal and ventral grps never work at the same time  reciprocal innervation
 Medullary centers
in the reticular formation of the medulla beneath the floor of the 4th
ventricle. It comprises 2 identifiable areas: the dorsal respiratory group
associated with inspiration & the ventral respiratory group associated with
expiration..
Dorsal respiratory group (DRG) of neurons:
• They are situated in the upper part of the medulla oblongata.
• All the neurons of this group are inspiratory neurons.
• Function: they are responsible for the basic rhythm of respiration.
• Dorsal resp grp  pacemaker
• sends signals downward to spinal cord  to diaphragm (intercostals &
abdominal muscles)  increase in size of chest.
• Sends signals to pneumotaxic center, stimulates it.
• When all known afferent stimuli are abolished the dorsal group generate
repetitive bursts of APs to the diaphragm & other inspiratory muscles. The
intrinsic activity starts with a latent period of several seconds, APs then
appear & increase in crescendo over the next few seconds. Inspiratory
muscle activity becomes stronger in a ramp type pattern. When the APs
cease the inspiratory muscle tone returns to preinspiratory level
 Ventral respiratory group (VRG) of neurons
• They are situated in the medulla oblongata, anterior &
lateral to the DRG neurons.
• This group has both inspiratory & expiratory neurons.
• The expiratory group is quiescent during quiet breathing
because ventilation is achieved by active inspiratory
muscle contraction & passive relaxation of the chest wall
to equilibrium position. However during exercise
expiration becomes active by increased activity in the
expiratory center.
• Ventral group neurons are inactive during quiet breathing
& become active during forced breathing, coughing (and
stimulate both inspiratory & expiratory muscles).
 Pontine Centers
• Pneumotaxic center:
• It is situated in the dorsolateral part in the upper pons
– It sends inhibitory impulses to the medullary inspiratory area which
shortens inspiration & increases breathing rate. It thus regulates
inspiration volume & respiratory rate
• Function:
• To control the medullary respiratory centers (particularly the
DRG) via the apneustic center.
• Pneumotaxic center  inhibits apneustic, so DRG neurons
are inhibited. Due to this, inspiration stops & expiration
starts.
• Thus, the pneumotaxic center influences the switching btwn
inspiration & expiration.
• It also increases the respiratory rate by reducing the duration
of inspiration.
 Apneustic Center
• The Apneustic centre – It is situated in the lower
pons.
• Function: It accelerates the activity of DRG
neurons which increases the depth of inspiration.
• Apneustic center  inspiration  can stimulate
dorsal resp grp.  facilitates resp  makes it
deeper.
– If the brain is sectioned just above this centre it
caused prolonged inspiratory gasps (apneuses)
interrupted by transient expiratory efforts. It has an
excitatory effect on the medullary inspiratory centre
tending to prolong the ramp action potentials.
 Inspiratory ramp
• It is the pattern of discharge from the DRG
neurons characterized by steady or gradual
increase in amplitude of the action potential
(in a ramp fashion).
• Significance: inspiratory ramp signals ensure
that there is a slow & steady inspiration
allowing the filling of lungs with air in a steady
manner.
 FACTORS AFFECTING THE RESPIRATORY CENTERS
Impulses from higher centers
• Afferents from higher centers: cortex and hypothalamus alter the respiration by
sending impulses directly to the DRG neurons.
Impulses from Stretch receptors in lung
Pulmonary stretch receptors
Lie within the airway smooth muscle & discharge in response to lung distension. Their
activity is sustained with lung inflation, i.e. they show little adaptation. Impulse travel in
large myelinated fibers of the vagus nerve. Leads to the Hering-Breuer inflation reflex
where inflation of the lungs inhibits further inspiratory muscle activity & deflation
initiates inspiratory activity. Largely inactive in humans unless tidal volume exceeds 1L.
• Hering-Breuer Reflex
• It is a protective reflex that restricts the inspiration & prevents overstretching of
lung tissues.
• It is initiated by stimulation of stretch receptors of air passage. These receptors are
situated in the wall of the bronchi & bronchioles.
• When tidal volume becomes more than 1L  stretching of the lungs  stimulation
of stretch receptors in air passage  transmission of impulses thru vagal afferents
to respiratory centers  inhibition of DRG  inhibition of respiration  start of
expiration & so the lungs are prevented from over-stretching.
 FACTORS AFFECTING THE RESPIRATORY CENTERS

Impulses from J receptors of lungs

• J receptors are juxtacapillary receptors present on the wall of the alveoli &
having close contact with the pulmonary capillaries.
• The stimulation of J receptors causes apnea. Apena is followed by
hyperventilation in patients effected by pulmonary congestion & left heart
failure.
• In the alveolar walls close to the capillaries “juxta-capillary”. Slow
nonmyelinated C fibers of the Vagus nerve. Engorgement of pulmonary
capillaries & increased interstitial fluid volumes of the alveolar wall activate
these receptors. May play a role in the rapid shallow breathing (sensation of
SOB) in heart failure.
Impulses from irritant receptors of lungs
• Irritant receptors are stimulated by irritant chemical substances.
• Lie between airway epithelial cells & are stimulated by noxious gases, cigarette
smoke, inhaled dusts & cold air. Vagal myelinated fibers  bronchoconstriction
& hyperpnea. Show rapid adaptation & may be involved in the
bronchoconstriction of asthma attacks.
• Stimulation of irritant receptors produces reflex hyperventilation along with
bronchospasm. This prevents further entry of harmful agents into the alveoli.
Impulses form proprioceptors
• Proprioceptors are the receptors which give response to change in
the position of the body.
• These receptors are situated in joints, tendons & muscles.
• Proprioceptors are stimulated during muscular exercise & send
impulses to the cerebral cortex which causes hyperventilation via
the medullary respiratory centers.
Impulses from thermoreceptors & pain receptors
• Thermoreceptors are cutaneous receptors which give response to
change in environmental temperature. When the body is exposed
to cold, the respiratory center causes hyperventilation.
• Stimulation of pain receptors also causes hyperventilation
Bronchial C-fibers
• Similar to the J receptors but present in the bronchial circulation.
They respond quickly & lead to rapid shallow breathing,
bronchoconstriction & mucous secretion.
 Other Receptors
• 1. Nose & Upper Airway Receptors The nose, nasopharynx,
larynx & trachea contain receptors that respond to mechanical &
chemical stimulation  sneezing, coughing &
bronchoconstriction. Laryngeal spasm may occur if the larynx is
irritated mechanically e.g. during endotracheal tube insertion.
• 2. Joint & Muscle Receptors Impulses from moving limbs
stimulates ventilation in the early stages of exercise.
• 3. Gamma System The intercostals muscles & diaphragm contain
muscle spindles that sense elongation. Used to reflexly control
the strength of contraction.
• 4. Arterial Baroreceptors BP stimulates aortic & carotid sinus
baroreceptors  reflex hypoventilation or apnea.
• 5. Pain & temperature Pain often causes a period of apnea
followed by hyperventilation. Heat causes hyperventilation
 Characterization of breathing activity.

• Eupnea: Normal respiration

• Tachypnea: increase in rate of respiration
• Bradypnea: decrease in rate of respiration
• Hyperpnea: Abnormal Increase in rate and depth of
respiration
• Hypopnea: Abnormal Decrease in rate and depth of
respiration
• Hyperventilation: vol. of exhaled CO2 is larger, PaCO2
decreases.
• Hypoventilation: vol. of exhaled CO2 is smaller than the rate
of CO2 production & PaCO2 rises.
• Dyspnea: difficult or labored breathing, and
• Apnea: temporary cessation of breathing (40-60 sec in
normal person)
 Forms of apnea
• Voluntary Apnea
– At the end of voluntary apnea, the subject is forced to breathe, which is called the
breaking point. It is bcoz of accumulation of CO2 in blood, which stimulates the
respiratory centers causing hyperventilation
• Apnea after hyperventilation
– It occurs due to lack of CO2. During hyperventilation, pCO2 in blood   no. of
stimuli to the respiratory centers  apnea
• Deglutition apnea
– The arrest of breathing during deglutition (swallowing). When the food passes thru the
pharynx, there is a possibility for it to enter the respiratory passage thru larynx causing
choking. This is prevented by the closing of larynx by backward movement of epiglottis
• Adrenaline Apnea
– Administration of adrenaline   BP  stimulation of the baroreceptors 
bradycardia & apnea
• Obstructive Apnea
– It occurs bcoz of obstruction in the respiratory tract due to excess tissue growth like
tonsils & adenoids. The most common obstructive apnea is the sleep apnea (common
in obese people)
• Central apnea
– It occurs due to brain disorders (seen in premature babies)
Chemical mechanism of regulation of respiration
• operated through the chemoreceptors.
– Chemoreceptors are the sensory nerve endings, which give
response to changes in chemical constituents of blood.
Changes which Stimulate Chemoreceptors
• Hypoxia (decreased pO2)
• Hypercapnea (increased pCO2)
• Increased hydrogen ion concentration.
Types of Chemoreceptors
• Central chemoreceptors: Central chemoreceptors are
the chemo-receptors present in the brain
• Peripheral chemoreceptors: Peripheral chemoreceptors
are the chemoreceptors present in carotid and aortic
region
 CENTRAL CHEMORECEPTORS
• Central chemoreceptors are connected with
respiratory centers, particularly the dorsal
respiratory group of neurons through
synapses. These chemoreceptors
• act slowly but effectively.
• Are responsible for 70% to 80% of increased
ventilation through chemical regulatory
mechanism.
• Main stimulant for central chemoreceptors is the
increased hydrogen ion concentration. However, if
hydrogen ion concentration increases in the blood, it
cannot stimulate the central chemoreceptors because, the
hydrogen ions from blood cannot cross the blood brain
barrier and blood-cerebrospinal fluid barrier.
• On the other hand, if carbon dioxide increases in the
blood, it can easily cross the blood-brain barrier and blood
cerebrospinal fluid barrier and enter the interstitial fluid of
brain or the cerebrospinal fluid.
– There, the carbon dioxide combines with water to form
carbonic acid. Since carbonic acid is unstable, it immediately
dissociates into hydrogen ion and bicarbonate ion
• Hydrogen ions stimulate the central
chemoreceptors.
• From chemoreceptors, the excitatory impulses
are sent to dorsal respiratory group of neurons,
resulting in increased ventilation (increased rate
and force of breathing).
– Because of this, excess carbon dioxide is washed out
and respiration is brought back to normal.
• Lack of oxygen does not have significant effect on
the central chemoreceptors, except that it
generally depresses the overall function of brain
 PERIPHERAL RECEPTORS
• Hypoxia is the most potent stimulant for peripheral
chemoreceptors.
– It is because of the presence of oxygen sensitive potassium
channels in the glomus cells of peripheral chemoreceptors.
• Hypoxia causes closure of oxygen sensitive potassium
channels and prevents potassium efflux.
– This leads to depolarization of glomus cells (receptor
potential) and generation of action potentials in nerve
ending.
• These impulses pass through aortic and Hering nerves
and excite the dorsal group of neurons.
• Dorsal group of neurons in turn, send
excitatory impulses to respiratory muscles,
resulting in increased ventilation.
– This provides enough oxygen and rectifies the lack
of oxygen.
• In addition to hypoxia, peripheral
chemoreceptors are also stimulated by
hypercapnea and increased hydrogen ion
concentration.
– However, the sensitivity of peripheral
chemoreceptors to hypercapnea and increased
hydrogen ion concentration is mild
 POST LECTURE ACTIVITIES
READING ASSIGNMENT
• Ventilation perfusion mismatch
• Diffusion of gases across membranes
• Pulmonary function tests
• Dynamic airway compression and equal pressure point
STUDY QUESTIONS
• Discuss the mechanics of breathing
• Discuss the lung function test parameters
• Discuss the factors for and against the collapse of an alveoli
• Discuss the transport of respiratory gases