RESPIRATORY PHYSIOLOGY

1. Cellular Respiration

2. O2 /CO2 carriage in blood

3. Mechanics of respiration

4. Gas exchange in the lung

5. Control of ventilation

6. Pulmonary circulation

7. Applied physiology

MCQs

Short answer questions

Viva
 Tips on answering SAQ

Q. Why? What? How?

* Definition

* Formula or Equation

* Measurement or Principles

* List and explanation

* Factors that increases or decreases

* Numbers or facts that are unique for the topic

* Effects of change

* Applied
* Graphs

Q. Write short notes on closing capacity

- Definition
Volume at which small airways begin to close (> 11th generation) in dependent
areas of the lung
(Normally depend on radial traction, caused by elastic recoil of surrounding tissues to
keep them open. Patency of these small airways is dependent on lung volume)

Closing Capacity = Residual Volume + Closing Volume

 Consequence of which, at low lung volumes, alveolar in dependent parts

continue to be perfused but not ventilated  intrapulmonary shunting  promotes
hypoxemia.

- Measurement of CC

 Use of tracer gas (Xenon 133) inhaled near RV, exhaled from TLC
 Single breath Nitrogen method
- 100% O2
- Rapid N2 analyzer
- Expired [N2} v volume of gas expired
- Airway closure start to occur when the expired N2 starts to rise
above plateau value (Phase 4)
(Due to – delayed washout of closed airways
- less ventilated apical alveolus; less dilute N2)
- Graph 1: [N2%] v lung volume
- Significance

At normal tidal breathing, in healthy adults, CC is well below FRC, increases with age
44 y o CC = FRC in supine
66 y o CC = or exceeds FRC in upright position

 Probably responsible for the age related decline in arterial O2 tension

- CC is not related to posture unlike FRC

- Graph 2: Lung volume v Age

Q. Draw an expiratory flow-volume curve for a forced expiration from
total lung capacity. Describe its characteristics in people with normal
lungs, obstructive and restrictive lung disease.
Briefly explain the physiological mechanisms involved in the concept
of flow limitation.

Dynamic airways compression/flow-related airways compression/ flow limitation

- Airways collapse when intrapleural pressure > intraluminal pressure

- Normally does not occur at normal tidal ventilation
- During forced ventilation, P intrapleural >> P intraluminal (declines along length of
airway due to high turbulent flow and airway resistance – reduced lung volume)
- Airways remain open to EQUAL PRESSURE POINT where P
intraluminal=intrapleural usually beyond 11th generation. Distal to this airway collapses
- Starling resistor mechanism
- Moves towards smaller airways as lung volume decreases
- At normal lung volumes, expiratory flow rates is effort independent, being limited
by airway compression rather than effort
- Dynamic airways compression is more likely when
- breathing at low volumes
- Airway resistance increase
- Elastic recoil diminished

GRAPH 1: Flow – volume loops

Obstructive – TLC higher

 - Max flow rates reduced
- descending limb is concave shaped
Q. Write short notes on pulmonary vascular resistance

- Low resistance circuit

- Pressure drop is ~ 10 mmHg. (m PAP= 15 mmHg, m LAP= 5 mmHg)
- PVR = 1/10 SV
PVR= (mean PAP – PCWP) X 80/CO
- Unit is Dynes.sec/cm5
- Normal value -100 Dynes.sec/cm5
- 3 major factors affect PVR
- Hypoxic pulmonary vasoconstriction
- Lung volume
- Pulmonary artery pressure

Hypoxic pulmonary vasoconstriction

- Local vasoconstrictive effects of low PAO2
- Shunts blood from under ventilated lungs
- Exact mechanism not known,? Local mediators
- Anesthetic significance - Volatile agents inhibit HPV
- Single lung ventilation

Lung volume
- At high and low lung volumes, PVR is INCREASED
- Total resistance is lowest at lung volumes = FRC
- Contributed by both alveolar and extra-alveolar vessels

Pulmonary artery pressure

- Increased PAP will cause a reduction in PVR via 2 mechanisms
- Recruitment i.e opening of previously closed pulmonary capillaries.
- Important if the PAP is initially low
- Distension of capillaries further when PAP increases

Other factors
- Hypercarbia
- Acidosis
- Hypoxemia
- Hypothermia
- Drugs e.g. volatile agents, vasodilators,

Graph; Resistance v lung volume

Q. Describe the factors that affect airways resistance

Airway resistance
- Friction between molecules of flowing gas and airway walls
- Calculated as Driving Pressure (mouth pressure – alveolar pressure)/ flow
rate.
- Ohm’s Law re-arranged: R= P/flow
- Unit is cmH2O/L/sec
- Normal value: 0.5-1.5 cmH2O/L/sec

Factors that affect resistance

Types of flow

- Laminar v turbulent flow

- Reynolds number > 2000, turbulent flow
- Increased density of gas, velocity and diameter of tubing, increases
turbulent flow  increase resistance
- Conversely decreased density of gas, velocity and diameter, reduces
resistance
- Laminar flow, (Hagen –Poiseuille’s Law), doubling of radius gives 16-fold
decrease in resistance. Despite smaller radius, smaller airways offer comparatively
little resistance because they are more in numbers and are in parallel.
Airway caliber is affected by

- Lung volume
- Increased smooth muscle
- Increased secretions
- Increased oedema
- Extrinsic compression

Effects of increased airway resistance

- Increased time to complete exhalation  increased FRC

- Active exhalation, increased WOB
- Dyspnoea
- To reduce resistance, patient will have to reduce rate of breathing, reduce
flow velocity, increase PEEP (pursed lips)  will reduce pressure gradient.

Graph
Time Constant

- Preferential ventilation, other than dependent on gravity, is also influenced

by differences between resistances and compliance of lung units.
- Both these factors produces regional differences in ventilation
- If RESISTANCE is increased, movement of air in and out of each lung unit,
will be slower
- If COMPLIANCE is reduced, flow to each lung unit will cease sooner
- THEREFORE, resistance and compliance affects the time-dependent filling or
emptying of units
- Can be expressed as;
Time constant = R X Cx
- Is used to describe the rate of change of an exponential process, and is THE
TIME AT WHICH THE PROCESS WOULD HAVE BEEN COMPLETE, HAD THE INITIAL RATE OF
CHANGE CONTINUED
- Emptying or filling is 95% complete after 3 time-constants
- Different lung units will have different time –constant, therefore, there can
still be flow of gas within lung units at the end of inspiration or expiration
- Regional ventilation will depend on frequency of ventilation.
Q. What are the physiological consequences of decreasing functional

residual capacity by one litre in an adult?

- Definition & values

- FRC = RV + ERV
- Normal is 30ml/kg (2.1litres in a 70kg adult male)
- Balance of the outward elastic recoil of the chest wall and the inward elastic recoil

- Consequences of reducing FRC by 1L in an adult

- Decreased O2 store
- Decreased O2 buffering capacity
- Decreased lung volume: 5 effects
- increased work of breathing (decreased lung compliance, increased early
airways closure)
- increased pulmonary vascular resistance
- increased airways resistance
- Atalectasis
- Increased V/Q mismatch
Q. List the physiological factors which increased respiratory rate. Include

a brief explanation of the mechanism by which each achieves the

increase.

- 3 most important factors

 Hypercapnoea - sensitive
- Minute-to-minute control by central (85%) and peripheral (15%)
chemoreceptor works synergistically with hypoxia (lower PaO2,
greater the increase in alveolar ventilation for incremental
increases in PaCO2)
 Hypoxia - not as an important in acute control
- needs to drop to 60mmHg before alveolar ventilation increases.
- Important in chronic lung disease
 Acidosis - mediated mainly by peripheral chemoreceptor(carotid body), if
PH drops low enough, BBB becomes permeable to H+ and central
chemoreceptor respond

- Other factors
- Exercise
- Voluntary control
- Pregnancy: greater change to tidal volume than respiratory rate
- Depression of central control: by opioid analgesics
Q. Describe the important determinants of works of breathing in an adult

human at rest. Explain how to minimize work of breathing 50%

Definition
- Work of Breathing: measured in L/cmH20, or the Joule
W : PxV
-WoB is divided into 2:

 Elastic work: is divided into surface tension (50-70%) and lung tissue (up to 50%)
: is performed in inspiration. Energy for expiration in quiet
breathing comes from the elastic work performs in inspiration and
stored elastically.
 Resistance work: is divided into viscous tissue resistance (20%) and airway
resistance (80%)
: is performed in both inspiration and expiration
- Expiration: passiveenergy for expiration has already been outlaid in inspiration
and stored elastically. Some energy is also lost as heat

-WoB will increase with an increase in any of the elements of Elastic work or
Resistance work
- Increase in WoB: decreased Surfactantis decreased in premature neonates,
prolonged ventilation and ARDS. Reduced compliance increased WoB.
- Viscous tissue resistance is the friction from lungs sliding over chest wall and
diaphragm sliding over abdominal organsreduced by pleural fluid and
peritoneal fluid
- Airway resistance is the resistance to gas flow in the airways. Increased in
turbulent flow and in a/ways with decreased radius e.g decr lung vol, oedema,
secretions, mscle tone, extrinsic compressions. Decreased by laminar flow,incr
lung vol, broncholidation.
- In COAD, Raw is increased. Increasing FRC, lung vol is increasedRaw(therefore
WoB) is decreased.
In pulmonary fibrosis, compliance is decreased and elastic work is increased
By increasing respiratory rate and decreasing tidal volume, although Raw is
increaseddecreased in elastic work (bec tidal vol is smaller, less elastic work is
performed) WoB decreased
Q Define `Venous Admixture’. Briefly explain how venous admixture
influences arterial O2 tension and how an increase in inspired O2
concentration may affect this.

Definition

~ is the theoretical amount of mixed venous blood which

would have to be added to pulmonary end-capillary blood, in
order to produce the observed drop in PaO2 from the PO2 in the
end-capillary blood.
- A calculated number and not an actual amount of mixed venous
blood.

In healthy adults, 2 main sources

 True Shunts (blood that enters the arterial system without passing
through ventilated areas of the lung, PO2 may be different to the PO2 of
mixed venous blood.)
- Bronchial circulation
< 1 % of CO
To pulm veins
May increase in lung disease

- Thebesian Veins
< 0.3% of CO
From walls to L ventricle

 V/Q mismatch (V/Q < 1)

Blood not fully oxygenated as it passes through poorly ventilated areas of
the lungs.
Venous admixture will cause a reduction in PaO2, compared with PO2
in end-pulmonary capillary.

Pulmonary blood, with its high PaO2 (~100mm Hg) is mixed with a
certain amount of deoxygenated venous blood, with a SO2 of about
75 mmHg and a lower resulting PaO2 of ~95mmHg is seen.

In areas of high V/Q matching, (apex) - high PaO2 but reduced perfusion,
O2 content can not increase anymore due to flat part of ODC. Contribution
of units with high V/Q ratios can be assessed by measuring physiologic
dead space using Bohr Equation.

Areas with low V/Q, (base of lung)- lower PO2 but higher perfusion,
therefore this region has a lower O2 content but contributes more to the
total pulmonary venous flow hence lowering of pulmonary venous and
arterial pO2 . Contribution with units of low V/Q ratios can be assessed by
measuring the physiologic shunt using Shunt Equation.

An index of the amount of shunting or V/Q mismatch is shown by the A-a

gradient.

Normally venous admixture, causing an increased A-a gradient does not

alter pCO2 as any increase is compensated centrally and peripherally by
increased alveolar ventilation with subsequent decrease in PCO2. CO2
dissociation curve is more linear

An increase in FIO2 will cause

- An increase PAO2 ( from the Alveolar Gas Equation )

- An increase in PaO2
- A slight increase in arterial O2 content
Contributed by the dissolved portion, chemical is fully
saturated

- A slight increase in mixed venous O2 content and O2

tension (50 mmHg)
- If the PvO2 is too high ( 100~mmHg as with hyperbaric therapy)
Absence of Haldane effect, therefore a rise in PvCO2.

Q Discuss the differences between the apex and the base of the lungs.
Differences present as a consequence of vertical gradients in pulmonary
perfusion and ventilation

Perfusion gradients are due to direct effects of gravity on hydrostatic

pressure. A difference of 30cmHg/23mmHg is seen between apex and
base of lung.

Ventilation gradients are due to indirect effects of gravity.

- Difference of 7.5 cmHg in intrapleural pressure due to weight of

the lung. ( -10cmHg v – 2.5cmHg )
- Alveolar size bigger at the apex; distend more due to more
negative intrapleural pressure
- Ventilation gradient better at the base due to favorable position
on the compliance curve compared to the apex.

Differences include:

- Alveoli at the apex are larger at end of expiration. Basal alveoli

are one-quarter the volume of apical alveoli at mid-expiration

- Lower ventilation at the apex due to

o larger size at end of expiration
o less favorable position on the compliance curve

- Lower perfusion at the apex compared to the base of lung due

to effects of gravity on hydrostatic pressure. PA pressure
decreases by 1.25mmHg/cm vertical distance up the lung.

- Higher V/Q at the apex of the lung ( 3.3 v 0.63)

- Higher PO2 at the apex compared to the base due to higher

V/Q ratio ( 132 v 89 )

- Lower PCO2 at the apex compared with the base due to higher
V/Q ratio ( 28 v 42 )

- As a consequence , pH is higher at the apex ( 7.51 v 7.39)

 - The differences in oxygen uptake and CO2 output results in a
higher respiratory exchange ratio at the apex (2) compared
to 0.67 at the base of the lung.

Graphs

Consequences of regional differences of ventilation and perfusion

- Areas of low and high V/Q ratios causing areas of dead space
ventilation and shunt, resulting in A-a difference

- Differences in regional perfusion causing 4 defined zones of blood

flow each with clinical significance
Q Describe the ways in which CO2 is carried in the blood

CO2 elimination is dependent on pulmonary blood flow and alveolar

ventilation.

CO2 is transported in the blood in several forms.

In plasma, CO2 is carried in 3 forms.

- A negligible amount of CO2 combines with amino group of

plasma proteins to form carbamino compounds.
Reaction restricted to one terminal amino group in each protein
and side-chain amino groups in lysine and arginine

R – NH2 + CO2  R – NH - COOH

- Remains in solution (solubility co-efficient is 0.03 mmol/L/mmHg

at 37 degrees celcius). 5% dissolves in plasma, 1 molecule of CO2
in 700 reacts with plasma water to form carbonic acid. Slow
reaction due to lack of carbonic anhydrase.

- Carbonic acid that is formed in plasma, dissociates into hydrogen

and bicarbonate ions (90%)

CO2 in physical solution determines blood pH. It is this form that most of
CO2 enters and exits the blood.

Most of CO2 produced passes into erythrocytes, where it is carried in 3

forms:

- negligible amount remains in solution in erythrocyte water

- Much larger amount of CO2 combines with hemoglobin to

form carboxyhemoglobin. Facilitated by the unloading of O2
from
Hemoglobin, which is 3.5 X more effective carrier than
Oxyhemoglobin. Combines with imidazole groups ( pKa-6.8) in the
38
histidine residues in Hb.

- Greatest amount of CO2 in the erythrocyte is hydrated to form

carbonic acid, which dissociates into H+ and HCO3- (about
99.9%).
Catalyzed by carbonic anhydrase (1000X faster than in plasma).
 Negatively charged HCO3 ions will diffuse out into plasma, in
exchange with chloride ( Hamburger effect/ Chloride shift ).
H+ ion
will be buffered by hemoglobin. More bicarbonate ions will be
produced.

CO2+H2O  H2CO3

H2CO3  H+ + HCO3-

Percentage contribution to a-v difference

Dissolved CO2 10%

Bicarbonate 60%
Carbamino 30%

CO2 Dissociation curve

Defines the relationship between total CO2 content and partial pressure of
CO2.

2 important differences exist between CO2 and O2 dissociation curves:

- CO2 dissociation curve is much more linear than O2

- The slope of CO2 dissociation curve is 3X steeper than O2,

meaning for a change in partial pressure, more CO2 than O2
can
be carried in the blood .

Degree of Hb oxygenation affects position of the CO2DC. The lower the O2

sat, the higher the CO2 content in the blood, for a given PCO2.  Haldane
Effect.

~ the increased ability of blood to carry CO2 when Hb gives up O2.

2 factors responsible for this are:

- DeoxyHb is 3.5X more effective then OxyHb in forming

Carbamino compounds. Accounts for 70% of the Haldane
Effect.

- DeoxyHb is a better buffer than OxyHb. Mops up more

of the H+
which are produced when H2CO3 dissociates. Improves
carriage of CO2 as bicarbonate. Accounts for 30% of
Haldane
effect.
Q Explain how oxygen supply of organs is maintained
during isovolaemic haemodilution.

Definition

- condition whereby RBCs per unit volume is decreased as a result of

lowered hemoglobin or increased in blood volume.
- One of the techniques for auto-transfusion. Blood is drawn off from a large
bore cannula and replaced with crystalloid (3:1 ratio) or colloids (1:1).
- Can also occur clinically , ie during fluid resuscitation in compensating
for hypovolaemic shock.

How?

- increased cardiac output

- increased blood flow generally
- increased local tissue perfusion
- increased ( maintaining ) O2 delivery at tissue level
- increased O2 extraction

• Haemodilution decreases O2 carrying capacity by decreases in

arterial O2 content, O2 delivery is usually maintained.
• O2 Flux ( D’O2) = CaO2 X C.O ( SV X HR )
o Preload – Frank-Starling)
o Afterload ) sympathetic result of relative hypoxia
o Contractility )
o Rate )

• Increased flow due to reduced viscosity ( improved rheology)

Poiseuille’s Law = PX pi X r (power of 4)
8X eta X length
• Local tissue hypoxia causes vasodilatation ( autoregulation)
• Hb-O2 dissociation Curve is shifted to the right at tissue level,
enhances unloading; decreased tissue PO2 means greater concentration
gradient.

• Hyperventilation ( increased PaO2)

• Erythropoietin ( long term )
• Increased FiO2 not important as physiological response.

Q Short notes on Surfactant

~ is a saturated phospholipids material that promotes alveolar

stability and expansion by lowering surface tension.
- synthesized by type II pneumocytes

Production

- under control of hypothalamic-pituitary-adrenal axis

- develop late in fetal life
- Type II pneumocytes differentiate at 24 weeks, begin to synthesize at
34 weeks
- Short half-life ( 14-48H )
- Sensitive to various influences that affect pulmonary integrity

Composition

o predominantly Dipalmityl phosphatidylcholine (80%)

o phosphatidylglycerol
o saturated phospholipids
o surfactant proteins ( SP-A,B,C,D )

o confined to a 50A layer on the alveolar surface

o hydrophobic and hydrophilic portions
o during expiration, surfactant molecules become densely packed,
repelling forces reduces alveolar surface tension

Relation to Laplace Law ( explain with alveolar with small and large radius)

Explain what happens when alveolar gets distended

Functions of Surfactant

- reduced surface tension with decreasing alveolar radius

- promotes alveolar stability
- anti-wetting effect
- improve lung compliance
- reduce work of breathing
- immunological
*bactericidal to some Gram positive bacteria in oral secretions
*opsonic agent that facilitate phagocytosis of Staph spp
*reduced toxicity of some inhaled substance by coating and altering its
composition or charge.

Clinical significance

Infants with RDS, use of intratracheal or nebulized bovine surfactant (beractant,

calfactant ) is available.
Q Describe the non-respiratory functions of the lung

Definition

Such functions include

- Blood reservoir
- Filter
- Metabolism :
- synthesis
- modification
- immunological and mechanical defence
- Heat exchanger
- Route of administration or elimination of drugs