Alveolar Capillary Unit

The Alveolar- Capillary Unit

Dimitar SajkovMD, DSc, PhD, FRACP

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 filteractivating and endocrine functionsfluid-balance regulator

Alveoli

Small, thin-walled, inflatable sacs at end of bronchiolesSurrounded by a jacket of pulmonary capillariesProvide thin barrier and enormous surface area for gas exchange by diffusionType II cells secrete surfactant


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 O2 and CO2 with the surrounding blood capillaries.


Structure


1 - Capillary

2 - Alveolus

3 - RBC

4 - Endothelium

5 - Basal Membrane

3

4

5

Gas Exchange

Gas Exchange - Diffusion

Gas Exchange

Partial Pressures of O2 and CO2 in the

body (normal, resting conditions): Alveoli

PO2 = 100 mm Hg

PCO2 = 40 mm Hg

Alveolar capillaries Entering the alveolar capillaries

PO2 = 40 mm Hg (relatively low because this blood has just

returned from the systemic circulation & has lost much of its O2)

PCO2 = 45 mm Hg (relatively high because the blood returning

from the systemic circulation has picked up CO2)

Gas Exchange

While in the alveolar capillaries, the diffusion of gasses occurs: O2 diffuses from the alveoli into

the blood & CO2 from the blood into the alveoli. Leaving the alveolar capillaries

PO2 = 100 mm Hg

PCO2 = 40 mm Hg

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

PO2 = 100 mm Hg

PCO2 = 40 mm Hg

Body cells (resting conditions)

PO2 = 40 mm Hg

PCO2 = 45 mm Hg

Because of the differences in partial pressures of O2 & CO2 in the systemic capillaries & the body cells, O2 diffuses from the blood & into the cells, while CO2 diffuses from the cells into the

blood. Leaving the systemic capillaries

PO2 = 40 mm Hg

PCO2 = 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

Gas Exchange

Non-Respiratory Functions of the Lung

Physical Filter

Chemical Filter

Activating Organ

Endocrine Organ

Fluid Balance regulator

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

Chemical Filter (John Vane’s theory)

Locally Acting (removed)

serotonin (90%) noradrenaline (35%) acetylcholine (95%) bradykinin (90%) angiotensin I (30%) PGE2 (95%)

PGF2a (95%) leukotrienes (95%) ATP, AMP (90+%)

Circulating (not affected)

dopamine adrenaline histamine vasopressin angiotensin II PGA2

substance P oxytocin eledoisin

Compliance

Measures the elastic characteristics, or “stretchiness” of the lungVaries with the degree of lung inflation and is different on inspiration or expiration

C = V/PDescribes how much lung inflation can be achieved by a unit pressure increase

Compliance

Surface Tension and Compliance

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

Surface Tension

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

Surface Tension in Lung Mechanics

A B

r = 1 cmr = 10 m = = 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/cm2

B) P = 2T/r = 2 x 72/10-3 = = 144,000 dyne/cm2 = = 80 cmH2O

1000 X the pressure is required to maintain B than A

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

Surfactant

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

Reduces “stiffness” of the lungsProtects patency of small airwaysPrevents total collapse of the alveoli (i.e. stabilises alveoli)Reduces work of breathingPrevents small alveoli emptying into larger ones

Roles of Surfactant

Roles of Surfactant

Prevents movement of fluid into the alveolus and keeps lungs dry (osmotic > hydrostatic pressure)

Acts as an anti-glueStimulates Lung host defence system: Immunosuppresses Acts as a chemotactic agent Opsonises bacteria Enhances mucous clearance

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 – lecithinS – Sphyngomyelin

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

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

Type II Alveolar Cell

Surfactant

Loss of Surfactant Function

Inhibition by serum proteins (albumin), fibrinogen, meconium, bilirubin and degradation products

Inactivation by O2 radicals and enzymes (phospholipases)

Decreased pool size due to lung injury

Mechanical factors (eg. Alveolar collapse)

Enhanced conversion to small aggregate forms of lipids

Interdependence

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 HCO3 and protein c.f. plasma]

Foetal breathing: development of neural control

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 T3 are also involved); aquaporins: water channel-forming proteins

The Foetal Lung

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

Surfactant - Acute Effects

Oxygenation improvement

Improved lung compliance

More uniform lung inflation

inflammation and implementation of lung defence mechanisms

Acute Lung Injury: A Condition Involving Impaired Oxygenation

Defined as: A ratio of the partial pressure of arterial

oxygenation (PaO2) to the fraction of inspired oxygen (FiO2) 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.

ARDS – Predisposing Factors

Direct InjuryInhalation Injury (i.e. Burns) Aspiration (i.e. chemical pneumonitis)

Indirect InjuryBacterial 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 %

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

Alveolar – Capillary Unit

Alveolar Capillary Unit

Documents

Transcript of Alveolar Capillary Unit