Ventilation and Gas Transport

Question 1

Describe and explain the main lung volumes found on a spirometry trace

Answer 1

Tidal Volume - Air inspired and expired in a normal breath
Inspiratory Reserve Volume - Air that can be inspired after a tidal inspiration
Expiratory Reserve Volume - Air that can be expired after a tidal expiration
Residual Volume - Air that cannot be expired due to the lung-chest wall interface
Functional Reserve Capacity - Air left in lungs after a tidal expiration at rest, ie. “default volume” - ERV + RV
Inspiratory Capacity - Maximum volume that can be drawn in from equilibrium FRC
Vital Capacity - Volume between minimum and maximum achievable goals
Total Lung Capacity - Everything

Question 2

Which factors affect the volumes found on a spirometry trace?

Answer 2

Mainly height, also genetics, age, aerobic fitness, disease, developmental altitude exposure.

Question 3

What is meant by dead space?

Answer 3

Parts of the airways that don’t participate in gas exchange. Physiological dead space = anatomical dead space + alveolar dead space

Question 4

Which parts of the airway are anatomical dead space

Answer 4

The entirety of the conducting airways and the upper respiratory tract (oral/nasal cavity, pharynx, larynx). 16 generations. Need to measure vol. with a known volume of inert gas - about 150mL.

Question 5

Describe what is meant by alveolar dead space

Answer 5

Respiratory tissue unable to participate in gas exchange due to absent/inadequate blood flow. In healthy individuals this is usually 0mL.

Question 6

What is pulmonary ventilation?

Answer 6

V(subscript)E is the amount of air moving in and out of the lungs per min. VE = Tidal Volume x Breathing Frequency

Question 7

What is alveolar ventilation?

Answer 7

V(subscript)alv is the amount of air reacing the gas exchange per min. This is the primary function of the alveolar tissue. Valv = (Tidal Volume - Dead Space) x Breathing Frequency

Question 8

Why aren’t intra-airway pressures as high as they are when they enter the lungs by forceful breathing?

Answer 8

Every generation in the airways has a divergence in the path which is associated with a 50% decrease in pressure and air velocity. This type of branching is dichotomous branching.

Question 9

How does inspiration happen?

Answer 9

Either the pressure outside the lung is increased (positive pressure breathing - patients on ventilation) or the pressure inside the lung is decreased (negative pressure breathing - normal). Inspiratory muscles (external intercostals and diaphragm) increase intrathoracic volume, decreasing pressure and air is sucked in from outside the body, and the lungs expand to fill the space.

Question 10

How does expiration happen?

Answer 10

When inspiration finished, the expansion of the chest wall force subsides, and the natural recoil of the lungs expels air from them

Question 11

How can airway resistance be calculated?

Answer 11

According to Poiseuille’s Law, resistance is proportional to the viscosity of a fluid (including air) and the length of the tube, and inversely proportional to r^4.
Resistance = 8 x eta(n with long leg) x L / pi x r^4

Question 12

How do the airways overcome this problem of resistance increasing as cross sectional area increases?

Answer 12

Constant generational divergence of airways means cumulative cross sectional area increases dramatically in small areas

Question 13

Describe the graph of resistance against airway generation

Answer 13

Starts at about 3 cm H2O per L per sec, and increases abit to about 3.5 (peak @ 4th gen) then decreases drastically to virtually 0.

Question 14

What is Fick’s Law of Distribution?

Answer 14

Molecules diffuse from high to low areas of concentration at a rate proportional to conc. grad, exchange surface area, diffusability of gas, and inversely proportional to thickness of exchange surface.
V(subscript)gas = A/T x D x [P1-P2]

Question 15

What is Henry’s Law?

Answer 15

That at any given temperature, the amount of gas that dissolves in a liquid is proportional to the solubility of the gas and the partial pressure of the gas in equilibrium with the liquid. C(subscript)DGas = alpha(solubility) x P(gas)

Question 16

What are the proportions of gasses making up atmospheric air?

Answer 16

78.2% N2, 20.-9% O2, 0.09% Ar, 0.04% CO2, and 0.01% inert gasses. % represents proportion of inspired air that contains each gas at sea level at barometric pressure (101.3kPa). Partial pressure of a gas in a mixture = p(barometric) x %

Question 17

What is therapaeutic O2 and who needs it?

Answer 17

Air with a higher O2 concentration, can sometimes reach up to 100%. Used for patients with lung disease - face mask or nasal cannula. Fraction of inspired O2 may reach > 60%, depending on conc. and flow rate. This increases the amount of O2 dissolved in the blood

Question 18

Why are noxious gases dangerous?

Answer 18

Because they have critically low O2 conc. or because they contain chemicals that interrupt normal physiology (Carbon Monoxide)

Question 19

How does an increase in altitude change the properties of inspired air?

Answer 19

Decrease in barometric pressure means that the partial pressure is lower. The gas fractions remain the same.

Question 20

How is the air travelling through the upper airways modified and why?

Answer 20

In order to protect lung tissue - respiratory conditioning. Occurs mostly in structures with high blood flow caudally to trachea (75%) or trachea only (25%). The air is warmed to physiological temp, humified to pH2O 6.3kPa (100% saturation), slowed, and mixed with air already in lungs. The lungs aren’t empty at the onset of tidal inspiration, the inspired air mixes with FRC - reducing O2 content and increasing CO2 content of air reaching alveoi.

Question 21

What does haemoglobin consist of?

Answer 21

4 haemoglobin monomers. Each monomer consists of a Haem group and a globin protein chain.
Each haem group is an Fe2+ molecule at the centre of a tetrapyrole porphyrin ring. This ligand reversibly binds one O2 molecule. Upon O2 binding, the Hb monomer undergoes confirmational change which makes other monomers more receptive to O2 molecules. This ability to change shape depending on ligand binding makes allosteric proteins

Question 22

Describe the storage of Hb

Answer 22

Hb is toxic - able to damage renal tubular epithelium - so packaged into enucleated cells known as erythryocytes. These cells are responsible for gas transport in the blood.

Question 23

What is the haematocrit?

Answer 23

The haematocrit is the proportion of blood that is erythrocytes. AKA. packed cell volume. Centrifuge a known volume of blood and the ratio of the total volume of the tube to the height of the cell pellet is the haematocrit. Usually about 40-50%.

Question 24

Explain the allosteric behaviour of Hb

Answer 24

As it becomes more saturated, it gains a greater affinity for O2. Fully deO2 Hb is in a tense state, it’s structure makes it difficult for O2 to bind. Every subsequent binding of O2 relaxes the Hb molecule, increasing affinity each time. With 3 O2 bound, affinity is 300x no O2s bound. When Hb is fully saturated, a binding site in the middle of the molecule between the 2 b chains is revealed, for 2,3-Diphosphoglycerate. This is a cofactor in rbc energy production, and it pushes the b chains into a tense state, promoting unloading

Question 25

Explain the shape of the Oxygen Dissociation Curve

Answer 25

The ODC is a sigmoid curve. In solution, the relationship between PO2 and dissolved O2 is linear. Across the physiological range of the lungs, Hb remains almost fully saturated - it has a shallow relationship. This means that a large change in PO2 = small change in HbO2. The reverse is true for respiring tissues - a small PO2 change = a large HbO2 change. This makes Hb loading O2 at the lungs and unloading in respiring tissues very efficient.

Question 26

What factors can change the appearance of the ODC?

Answer 26

Conditions associated with low O2 - also exercise. Increased H+ conc - deoxyHb is stabilised ie. in the tense state so O2 affinity is reduced.
Increased temp because it denatures O2-Hb bond (not very noticable).
Increased CO2 (hypercapnia) - CarbaminoHb stabilises deoxyHb and also H+ increase due to carbonic acid
Increased 2,3-DPG - binds Hb and rearranges into tense state.
All these conditions are associated with exercise, which is good because we want more dissociation at any pO2. These all result in the curve shifting right - Bohr shift

Question 27

What effect does increased/decreased O2 carrying capability have on the ODC

Answer 27

Polycythaemia is a condition where rbc conc. is much higher than normal ie. haematocrit is >55%. This stretches the graph upwards. Standard ODC assumes 150g/L Hb. The graph is stretched up because for any PO2, there is no increase in Hb saturdation, but an increase in total O2 in blood. The reverse is true for anaemia, the ODC is pushed down. Anaemic patient might have a normal pulse oximetry, as they can carry O2 in Hb normally, they just don’t have enough Hb.

Question 28

Why is using deoxygenated blood when referring to venous blood not totally accurate?

Answer 28

It has about 75% O2 of arterial blood. A better term is mixed venous blood (v with a line ontop). It retains this much O2 as O2 demand is low at rest.

Question 29

What are the partial pressures of O2 in venous and arterial blood?

Answer 29

Using ODC, 75% O2 of arterial blood corresponds to 5.3kPa for venous blood, and partial pressure of O2 in arteries is 13.5kPa. When “deO2” blood reaches gas exchange surface it equilibriates in 0.25secs

Question 30

Describe the path of O2 during oxygenation

Answer 30

O2 diffuses passively down a conc. grad - from the alveolar space, into pulmonary epithelial cells, into the interstitial space, into vascular endothelial cells, into the plasma, into the rbc, and binds Hb that’s not saturated.

Question 31

Describe the contents of the arteries after the gas exchange event

Answer 31

Post-alveolar arteries have pO2 = PO2 in alveoli (13.5kPa). The saturation of Hb with O2 reaches 100% with HbO2 conc. = 20.1mL/dL and the conc. dissolved O2 in arteries is 0.34mL/dL.

Question 32

Describe unloading of O2 in the tissues

Answer 32

At the systemic capillary beds, tissue PO2 &laquo_space;P(arterial)O2. This promotes diffusion of O2 down conc. grad from plasma into endothelia, interstitium, respiring cells, mitochondria. As P(arterial)O2 decreases more, Hb offloads O2 and the O2 follows the dissolved O2 down conc. grads into the mitochondria. Once this blood enters the venous circulation, PO2 = 5.3% and saturation of O2 = 75%. Conc. dissolved O2 is reduced to 0.14mL/dL and HbO2 to 15mL/dL. This a 5mL/dL reduction - termed Oxygen flux. This is O2 consumption - VO2 (250mL/min)

Question 33

Describe the loading of CO2 in the lungs

Answer 33

CO2 is 20x more soluble than O2. CO2 diffuses into the plasma quickly, creating carbonic acid, which dissociates, dropping blood pH slowly below 7.4. As plasma pCO2 increases, CO2 diffuses into rbcs where carbonic anhydrase creates carbonic acid at a 5000x rate - increasing the rate of dissociation.

Question 34

What does the AE1 exchanger do?

Answer 34

Pumps out HCO3 from carbonic acid out of rbc and imports Cl to maintain to electroneutrality (chloride shift). This influx is associated with H2O influx, which is useful to keep the cells hydrated (HCO3 contains water).

Question 35

How is the pH of the blood maintained?

Answer 35

The beta globin protein chains of Hb have certain residues eg. Histamine that accept protons.

Question 36

What is carbaminoHb?

Answer 36

Some intra-rbc CO2 binds to Hb, but not to the haem group in the same way as O2. It binds to the amine group and N terminal of globin chains (changing NH2 to NHCOOH).

Question 37

How is CO2 unloaded in the lungs?

Answer 37

CO2 diffuses into the alveoli, triggering the reversal of all other binding mechanisms. HCO3 goes back into the rbc and associates with H+ to form carbonic acid which is then broken down into CO2 and water. CO2 leaves the capillary by diffusion.

Question 38

What is COPD?

Answer 38

A condition which involves block/collapsed airways, resulting in a Residual Volume of >1.2L. This is because the alveoli contains air, but the airway is collapsed.

Question 39

What are some symptoms of COPD?

Answer 39

Reduced capacity for exercise ie. get breathless from simple tasks. This is because reduced lung function means that her lungs cannot O2 to the body quick enough.

Question 40

How would COPD present on an X-Ray?

Answer 40

Visible airways - not full of air so bad. Curved ribcage - hyperinflated lungs.

Question 41

How does COPD decrease ventilation?

Answer 41

V = A x D x driving P / T. Surface area decreases because lung is broken down. Driving pressure might decrease. Lower pO2 pushes fluid out of the lungs into the alveoli, essentially thickening the gas exchange surface.