Respiratory Physiology

1
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiration
Ventilation:
Action of breathing with muscles and lungs.

Gas exchange:
Between air and capillaries in the lungs.
Between systemic capillaries and tissues of the
body.

02 utilization:
Cellular respiration in mitochondria.

2
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Ventilation
Mechanical process that
moves air in and out of the
lungs. Insert 16.1

Diffusion of…
O2: air to blood.
C02: blood to air.

Rapid:
large surface area
small diffusion distance.
3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory structures

4
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Conducting Zone

Conducting zone:
All the structures air Insert fig. 16.5
passes through
before reaching the
respiratory zone.

Mouth,nose, pharynx,
trachea, glottis,
larynx, bronchi.

5
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Conducting Zone

Conducting zone

Warms and humidifies until inspired air becomes:

37 degrees
Saturated with water vapor

Filters and cleans:

Mucus secreted to trap particles
Mucus/particles moved by cilia to be expectorated.

6
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory Zone

Respiratory zone

Region of gas exchange between air and

blood.

- bronchioles
- alveoli

7
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory Zone

8
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory Zone
Alveoli
Air sacs
Honeycomb-like clusters
~ 300 million.
Large surface area (60–80 m2).
Each alveolus: only 1 thin cell layer.
Total air barrier is 2 cells across (2 m) (alveolar
cell and capillary endothelial cell).

9
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Respiratory Zone

Alveolar cells:

Alveolar type I: structural cells.

Alveolar type II: secrete surfactant.

10
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mechanics of breathing

11
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Thoracic Cavity
Diaphragm:
Sheets of striated muscle divides anterior body
cavity into 2 parts.

Above diaphragm: thoracic cavity:

Contains heart, large blood vessels, trachea,
esophagus, thymus, and lungs.

Below diaphragm: abdominopelvic cavity:

Contains liver, pancreas, GI tract, spleen, and
genitourinary tract.

12
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mechanics of breathing
Gas: the more volume, the less pressure (Boyle’s law).

Inspiration:
lung volume increase ->
decrease in intrapulmonary pressure, to just below
atmospheric pressure ->
air goes in!

Expiration: viceversa

13
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mechanics of breathing
Intrapleural space:
“Space” between visceral and parietal
pleurae.
Visceral and parietal pleurae (membranes) are
flush against each other.
Lungs normally remain in contact with the chest
walls.
Lungs expand and contract along with the
thoracic cavity.

14
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pleura

15
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mechanics of breathing
Compliance: lungs can stretch when under tension.

Elasticity: they recoil (to original shape).

- elastin

16
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Inspiration
Inspiration

Diaphragm contracts -> increased thoracic volume

vertically.
Intercostals contract, expanding rib cage ->
increased thoracic volume laterally.
Active

More volume -> lowered pressure -> air in.

Negative pressure breathing.
17
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Expiration

Expiration

Due to recoil of elastic lungs.

Passive.

Less volume -> pressure within alveoli is just above

atmospheric pressure -> air leaves lungs.

Note: Residual volume of air is always left behind, so

alveoli do not collapse.

18
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Mechanics of breathing
Quiet breath: +/- 3 mmHg
intrapulmonary pressure.

Forced breath:
Extra muscles, including abs
+/- 20-30 mm Hg intrapulmonary pressure

19
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Problems
Pneumothorax: a hole in chest can cause
one lung to collapse.

20
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Surface tension

21
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Surface Tension

Very thin film of fluid in alveoli.

Absorb: Na+ active transport.
Secrete: Cl- active transport.

22
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Surface Tension

Surface tension:
H20 molecules at the surface are attracted to
other H20 molecules rather than to air.

Surface tension-> hard to expand the

alveoli.
Small alveoli, more resistance to expansion.

23
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Surface tension
Surfactant
produced by alveolar type II cells.
Interspersed among water molecules.
Lowers surface tension.

RDS, respiratory distress syndrome, in preemies.

First breath: big effort to inflate lungs!

24
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Surface tension

Insert fig. 16.12

25
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Measuring pulmonary function

26
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pulmonary Function
Spirometry:
Breathe into a closed system, with air,
water, moveable bell

Insert fig. 16.16

27
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lung volumes
Tidal volume (TV): in/out with quiet breath (500
ml)

Total minute volume: tidal x breaths/min

6 L/min
Exercise: even 200 L/min!

Anatomical dead space:

Conducting zone
Dilutes tidal volume, by a constant amount.
Deeper breaths -> more fresh air to alveoli.
28
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lung volumes

Inspiratory reserve volume (IRV): extra (beyond

TV) in with forced inspiration.

Expiratory reserve volume (ERV): extra (beyond TV)

out with forced expiration.

Residual volume: always left in lungs, even with forced

expiration.
Not measured with spirometer

29
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lung capacities

Vital capacity (VC): the most you can actually

ever expire, with forced inspiration and
expiration.
VC= IRV + TV + ERV

Total lung capacity: VC plus residual volume

30
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pulmonary disorders

31
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pulmonary disorders Stop

Restrictive disorder:
Vital capacity is reduced.
Less air in lungs.

Obstructive disorder:
Rate of expiration is reduced.
Lungs are “fine,” but bronchi are obstructed.

32
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders
Restrictive disorder:
Black lung from coal mines.
Pulmonary fibrosis: too much connective tissue.

33
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pulmonary Disorders

COPD (chronic obstructive pulmonary

disease):
Asthma
Emphysema
Chronic bronchitis

34
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders
Obstructive disorder:

FEV = forced expiratory

Insert fig. 16.17
volume.

FEV1 = % of vital capacity

expired in 1st second.

Disorder if FEV1 is < 80%

Note: same total amount

expired.
35
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders

Asthma:
Obstructive
Inflammation, mucus secretion, bronchial
constriction.
Provoked by: allergic, exercise, cold and dry air
Anti-inflammatories, including inhaled epenephrine
(specific for non-heart adrenergic receptors),
anti-leukotrienes, anti-histamines.

36
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders
Emphysema:
Alveolar tissue is destroyed.
Chronic progressive condition
Cigarette smoking stimulates macrophages and WBC
to secrete enzymes which digest proteins.
Or: genetic inability to stop trypsin (which digests
proteins).

37
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

38
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases
Barometers use mercury (Hg) as
convenience to measure total atmospheric
pressure.

Sea level: 760 mm Hg (torr)

39
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

Total pressure of a gas mixture is = to the sum of the

independent, partial pressures of each gas (Dalton’s
Law).

In sea level atmosphere:

PATM = 760 mm Hg = PN + P0 + PC0 + PH 0 2 2 2 2

40
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

Partial pressures: % of that gas x total pressure.

In atmosphere:
02 is 21%, so (.21 x 760) = 159 mm Hg = P02

Note: atmospheric P0 decreases on a mountain,

2

increases as one dives into the ocean.

41
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases
But inside you, the air is saturated with water vapor.
PH20 = 47 mm Hg at 37 degrees

P0 :
So, inside you, there is less 2

P0 = 105 mm Hg in alveoli.
2

In constrast, alveolar air is enriched in CO2, as

compared to inspired air.
PCO = 40 mm Hg in alveoli.
2

42
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

Insert fig. 16.20

43
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

Gas and fluid in contact:

[Gas] dissolved in a fluid depends directly on its partial
pressure in the gas mixture.
With a set solubility, non changing temp.
(Henry’s law)

So…
P0 in alveolar air ~ = P0 in blood.
2 2

44
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

O2 electrodes can measure dissolved O2 in a fluid.

(also CO2 electrodes.)

Good index of lung function.

Arterial P0 is only slightly below alveolar P0

2 2

Arterial P0 = 100 mm Hg
2

Alveolar P0 = 105 mm Hg
2

P0 level in the systemic veins is about 40 mm Hg.

2

45
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases

46
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood gases
Most O2 is in hemoglobin

.3 ml dissolved in plasma +
19.7 ml in hemoglobin
20 ml O2 in 100 mls blood!

But: O2 in hemoglobin-> dissolved -> tissues.

Breathing pure O2 increases only the dissolved

portion.
- insignificant effect on total O2
- increased O2 delivery to tissues
47
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Pulmonary Circulation
L ventricle pumps to entire body, R ventricle
only to lungs.
Both ventricles pump 5.5 L/min!

Pulmonary circulation: various adaptations.

as a mellow river, doesn’t spill over the banks
low pressure, low resistance.
prevents pulmonary edema.
pulmonary arteries dilate if P02 is low (opposite of systemic)
48
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural control

49
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural control
Respiratory centers

In hindbrain Insert fig. 16.25

- medulla oblongata
- pons

automatic breathing

50
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural control

I neurons = inspiration
E neurons = expiration

I neurons -> spinal motor neurons ->

respiratory muscles.

E neurons inhibit I neurons.

51
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural control

Also: voluntary breathing controlled by

cerebral cortex.

52
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural control
Ondine’s curse: only voluntary breathing.

Ondine: “water nymph, punished by gods, must stay awake in order

to breath.”
Or: she so cursed her philandering husband, after she gave up
immortality to join him, and he promised to love her with every
waking breath…
http://www.silentpartners.org/sleep/sinfo/miscl/ondine.htm

Gene mutation in fetus:

http://news.bbc.co.uk/1/hi/health/2996791.stm

Description:
http://www.medterms.com/script/main/art.asp?articlekey=9634
53
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chemoreceptors
Oxygen: large “reservoir” attached to hemoglobin.

So chemoreceptors are more sensitive to changes in

PC02 (as sensed through changes in pH).

Ventilation is adjusted to maintain arterial PC02 of 40

mm Hg.

Chemoreceptors are located throughout the body (in

brain and arteries).

54
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

chemoreceptors

55
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

56
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Each hemoglobin has 4 polypeptide chains (2 alpha, 2

beta) and 4 hemes (colored pigments).

In the center of each heme group is 1 atom of iron

that can combine with 1 molecule 02.
(so there are four 02 molecules per hemoglobin
molecule.)

280 million hemoglobin molecules per RBC!

57
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

58
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin
Oxyhemoglobin:
Ferrous iron (Fe2+) plus 02.

Deoxyhemoglobin:
Still ferrous iron (reduced).
No 02.

59
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Carboxyhemoglobin:
carbon monoxide (CO) binds to heme instead
of 02

- smokers

60
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Can tell % of types of hemoglobin by color!

61
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin
Loading:
Load 02 into the RBC.
Deoxyhemoglobin plus 02 -> Oxyhemoglobin.

Unloading:
Unload 02 into the tissues.
Oxyhemoglobin -> deoxyhemoglobin plus 02.

62
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Loading/unloading depends on:

- P0 2

- Affinity between hemoglobin and 02

- pH
- temperature

63
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Dissociation curve: % oxyhemoglobin

saturation at different values of P0 . 2

Describes effect of P0 on loading/unloading. 2

Sigmoidal
At low P0 small changes produce large
2

differences in % saturation and unloading.

Exercise: P0 drops, much more unloading from veins.
2

At high P0 slow to change.

2

64
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Oxyhemoglobin Dissociation
Curve

Insert fig.16.34

65
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

66
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Affinity between hemoglobin and 02:

- pH falls -> less affinity -> more unloading

(and viceversa if pH increases)

- temp rises -> less affinity -> more unloading

exercise, fever

67
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Arteries: 97% saturated (i.e. oxyhemoglobin)

Veins: 75% saturated.

Arteries: 20 ml 02 /100 ml blood.

Veins: ~ 5 ml less

Only 22% was unloaded!

Reservoir of oxygen in case:
- don’t breathe for ~5 min
- exercise (can unload up to 80%!)
68
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Fetal hemoglobin (F):

- gamma chains (instead of beta)
- more affinity than adult (A) hemoglobin

69
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Anemias

70
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hemoglobin

Anemia:
[Hemoglobin] below normal.

Polycythemia:
[Hemoglobin] above normal.
Altitude adjustment.

71
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders

Sickle-cell anemia:
fragile, inflexible RBC
inherited change: one base pair in DNA -> one aa in
beta chains
hemoglobin S
protects vs. malaria; african-americans

Thalassemia:
defects in hemoglobin
type of anemia
72
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Disorders

73
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

RBC

74
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

RBC

RBC
no nucleus
no mitochondria

Cannot use the 02 they carry!!!

Respire glucose, anaerobically.

(note: androgens stimulate erythropoiesis)

75
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Transport of CO2

76
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

C02 Transport

H20 + C02 H2C03 H+ + HC03-

carbonic acid bicarbonate

77
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

C02 Transport

C02 transported in the blood:

- most as bicarbonate ion (HC03-)
- dissolved C02
- C02 attached to hemoglobin
(Carbaminohemoglobin)

78
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

C02 Transport
Carbonic anhydrase in RBC promotes useful
changes in blood PC02

CA
H20 + C02 -> H2C03 -> HC03-
high PC0 2

CA
H20 + C02 <- H2C03 <-
HC03- low PC0 2
79
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

C02 Transport

Chloride shift:
Chloride ions help maintain electroneutrality.

HC03- from RBC diffuses out into plasma.

RBC becomes more +.
Cl- attracted in (Cl- shift).
H+ released buffered by combining with
deoxyhemoglobin.

Reverse in pulmonary capillaries

80
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Acid-base balance

81
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Acid-Base Balance
Ventilation is normally adjusted to keep pace
with metabolic rate, so homeostasis of blood
pH is maintained.

82
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Acid-Base Balance
Hyperventilation -> PC0 down -> pH of CSF up -> 2

vasoconstriction -> dizziness.

If hyperventilating, should you breath into paper

bag? Yes! It increases PC0 ! 2

Metabolic acidosis can trigger hyperventilation.

Diarrhea -> acidosis.

Vomit -> alkalosis.

83
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Adaptations

84
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Exercise

During exercise, breathing becomes deeper and more rapid.

Yet blood gas levels instantly stay about the same. Huh?!

Neurogenic: sensory response from muscles?

Humoral: homones?
Local differences we can’t sense in a lab?

85
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Adaptations

Frequent exercise, or high altitudes ->

series of changes in oxygen
consumption, or [hemoglobin], etc.

86