Alveolar Capillary Unit

1. The Alveolar- Capillary Unit
Dimitar Sajkov
MD, DSc, PhD, FRACP

2. Alveolar - Capillary Unit

3. Alveolar - Capillary Unit
Complex cardiovascular system with
multiple functions:
Gas exchange
Oxygen sensing and redistribution of
pulmonary blood flow
Non-respiratory functions
physical and chemical filter
activating and endocrine functions
fluid-balance regulator

4. Alveoli
Small, thin-walled, inflatable sacs at end of
bronchioles
Surrounded by a jacket of pulmonary
capillaries
Provide thin barrier and enormous surface
area for gas exchange by diffusion
Type II cells secrete surfactant

5. Alveolar - Capillary Unit

6. Alveolar - Capillary Unit
A scanning electron
micrograph of the alveoli.
Humans have a thin layer
of about 700 million
alveoli within their lungs.
This layer is crucial in the
process called respiration,
exchanging O
2
and CO
2

with the surrounding
blood capillaries.

8. Alveolar - Capillary Unit
Structure

9. Alveolar - Capillary Unit
1 - Capillary
2 - Alveolus
3 - RBC
4 - Endothelium
5 - Basal Membrane
3
4
5

10. Gas Exchange

11. Gas Exchange - Diffusion

12. Gas Exchange
Partial Pressures of O
2
and CO
2
in the body
(normal, resting conditions):
·Alveoli
·PO
2
= 100 mm Hg
·PCO
2
= 40 mm Hg
·Alveolar capillaries
·Entering the alveolar capillaries
·PO
2 = 40 mm Hg (relatively low because this blood has just returned
from the systemic circulation & has lost much of its O
2
)
·PCO
2
= 45 mm Hg (relatively high because the blood returning from
the systemic circulation has picked up CO
2
)

13. Gas Exchange
While in the alveolar capillaries, the diffusion of
gasses occurs: O
2
diffuses from the alveoli into
the blood & CO
2
from the blood into the alveoli.
·Leaving the alveolar capillaries
·PO
2
= 100 mm Hg
·PCO
2
= 40 mm Hg

14. Gas Exchange
Blood leaving the alveolar capillaries returns to the left atrium & is
pumped by the left ventricle into the systemic circulation. This
blood travels through arteries & arterioles and into the systemic, or
body, capillaries. As blood travels through arteries & arterioles, no
gas exchange occurs.
·Entering the systemic capillaries
·PO
2
= 100 mm Hg
·PCO
2 = 40 mm Hg
·Body cells (resting conditions)
·PO
2 = 40 mm Hg
·PCO
2
= 45 mm Hg

15. Because of the differences in partial pressures of O
2
& CO
2
in the
systemic capillaries & the body cells, O
2
diffuses from the blood &
into the cells, while CO
2
diffuses from the cells into the blood.
·Leaving the systemic capillaries
·PO
2
= 40 mm Hg
·PCO
2
= 45 mm Hg
Blood leaving the systemic capillaries returns to the heart (right
atrium) via venules & veins (and no gas exchange occurs while
blood is in venules & veins). This blood is then pumped to the lungs
(and the alveolar capillaries) by the right ventricle.
Gas Exchange

16. Gas Exchange

17. Non-Respiratory Functions of the Lung
Physical Filter
Chemical Filter
Activating Organ
Endocrine Organ
Fluid Balance regulator

18. Physical Filter
All particles larger than red blood cells
(e.g. bubbles, clots, fat cells, fibrin)
Role in removing damaged white cells
Rapidly cleared by phagocytosis and
proteolytic enzymes

19. Chemical Filter (John Vane’s theory)
Locally Acting (removed)
serotonin (90%)
noradrenaline (35%)
acetylcholine (95%)
bradykinin (90%)
angiotensin I (30%)
PGE
2
(95%)
PGF
2a
(95%)
leukotrienes (95%)
ATP, AMP (90+%)
Circulating (not affected)
dopamine
adrenaline
histamine
vasopressin
angiotensin II
PGA
2
substance P
oxytocin
eledoisin

20. Compliance
Measures the elastic
characteristics, or
“stretchiness” of the
lung
Varies with the degree
of lung inflation and is
different on inspiration
or expiration
C = DV/DP
Describes how much lung inflation can be achieved by a
unit pressure increase

21. Compliance

22. Surface Tension and Compliance
Kurt von Neergard (1929)
suggested that ST was less than
that of water and that surface
active substances were present

23. Surface Tension
75% of tendency of the lung
to collapse is due to surface
tension (ST) at the gas-liquid
interface

24. Surface Tension in Lung Mechanics
A
B
r = 1 cm
r = 10 mm =
= 10 x 10
-4
cm
Assume ST is constant at 72 dyne/cm
Law of Laplace: P = 2T/r
A) P = 2T/r = 2 x 72/1 =
= 144 dyne/cm
2
B) P = 2T/r = 2 x 72/10
-3
=
= 144,000 dyne/cm
2
=
= 80 cmH
2
O
1000 X the pressure is required
to maintain B than A

25. Alveolar Surface Tension Forces
Attraction of liquid molecules produces
surface tension (ST), which
draws liquids closer together
resists force that would increase the area of the surface
ST is reduced by surfactant

26. Surfactant
Phospholipid produced by
type II alveolar cells
¯ surface tension in
alveoli
­ total lung compliance
­ lung “stability”

27. Reduces “stiffness” of the lungs
Protects patency of small airways
Prevents total collapse of the alveoli (i.e.
stabilises alveoli)
Reduces work of breathing
Prevents small alveoli emptying into larger
ones
Roles of Surfactant

28. Roles of Surfactant
Prevents movement of fluid into the alveolus
and keeps lungs dry (osmotic > hydrostatic pressure)
Acts as an anti-glue
Stimulates Lung host defence system:
Immunosuppresses
Acts as a chemotactic agent
Opsonises bacteria
Enhances mucous clearance

29. Surfactant Composition
Phospholipids 80%
dipalmitoyphosphatidylcholine (DPCC) 60%
Phosphatidylglycerol/ethanolamine/inositol 20%
Neutral Lipids 10%
Mostly Cholesterol
Surfactant Proteins 10%
SP-A; SP-D: hydrophilic
SP-B; SP-C: hydrophobic
L/S ratio: predictor of foetal lung maturity
L – lecithin
S – Sphyngomyelin

30. Surfactant Proteins
SP-A: Hydrophilic
formation of tubular lattice
regulatory function
defence function
SP-B: Hydrophobic
re-formation of layer after compression
SP-C: Hydrophobic
spreading function
SP-D: Hydrophilic
regulatory function
defence function

31. Surfactant Metabolism
Produced, stored and secreted by type II
alveolar cells and Clara cells
Half-time for turnover 5 - 10 hours
90% recycled by type II pneumocytes
10% cleared by alveolar macrophages
SP-A is primary regulator of metabolism and
lung defence mechanisms

32. Type II Alveolar Cell

33. Surfactant

34. Loss of Surfactant Function
Inhibition by serum proteins (albumin), fibrinogen,
meconium, bilirubin and degradation products
Inactivation by O
2
radicals and enzymes
(phospholipases)
Decreased pool size due to lung injury
Mechanical factors (eg. Alveolar collapse)
Enhanced conversion to small aggregate
forms of lipids

35. Interdependence

36. Interdependence

37. The Foetal Lung
Airways formed by week 16
Alveoli start to form ~ at week 20; ~20 million
alveoli present at birth
Alveolar type II cells appear ~ at week 24
Foetal lung fluid (5 ml/kg/hr) maintains lung at
FRC [high Cl
-
, low HCO
3
and protein c.f. plasma]
Foetal breathing: development of neural control

38. Amniocentesis: phosphatidylcholine increases
rapidly after ~ 33 wk
Lecithin/Sphingomyelin ratio + 2.0 at ~ 35 wk
80% of infants < 30 wk have RDS
45% of infants < 32 wk have RDS
At birth:
adrenaline activates Na channels in type II cell
(vasopressin, cortisol and T
3
are also involved);
aquaporins: water channel-forming proteins
The Foetal Lung

39. Not conducive to gas exchange
 Thick blood gas barrier
 Low compliance
 Immature epithelial cells
 Low surfactant levels
 Small area for gas exchange
 Poorly vascularized
 High resistance to blood flow
Conducive to gas exchange
 Thin blood gas barrier
 Highly compliant
 Mature epithelial cells
 Adequate surfactant
 Large area for gas exchange
 Highly vascular
 Low resistance to blood flow
Immature lung
Mature lung

40. Surfactant - Acute Effects
Oxygenation improvement
Improved lung compliance
More uniform lung inflation
¯ inflammation and implementation
of lung defence mechanisms

41. Acute Lung Injury: A Condition
Involving Impaired Oxygenation
Defined as:
A ratio of the partial pressure of arterial oxygenation
(PaO
2) to the fraction of inspired oxygen (FiO
2) that
is < 300 regardless of whether or how much positive
end-expiratory pressure is used to provide respiratory
support
Bilateral pulmonary infiltrates on chest radiograph
Pulmonary Artery Occlusion Pressure of < 18 mmHg
or no clinical evidence of elevated left atrial pressure
When the injury is “severe”, we have recognizable
clinical features of ARDS.

42. ARDS – Predisposing Factors
Direct Injury
Inhalation Injury (i.e. Burns)
Aspiration (i.e. chemical pneumonitis)
Indirect Injury
Bacterial Sepsis (i.e. endotoxemia)
Pancreatitis
With some of these “predisposing conditions”, the risk of
A.R.D.S. is substantial
Gastric Aspiration & Sepsis: Overall Mortality of 30 - 40 %

43. ARDS - Management
Measures to correct the abnormality in vascular
permeability or to limit the degree of inflammatory
reaction present in ARDS, do not exist.
Clinical management involves primarily supportive
measures aimed at maintaining cellular and physiologic
function, while the acute lung injury resolves.
What cellular functions are you trying to maintain ?
Alveolar Gas Exchange
Organ Perfusion
Aerobic Metabolism

44. Alveolar – Capillary Unit