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.
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.
24. Surface Tension in Lung Mechanics r = 1 cm r = 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/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 A B
Von Neergaard, using excised lungs filled with air or liquid, demonstrated that “in all states of expansion surface tension was responsible for a greater part of lung elastic recoil than was tissue elasticity”. Von Neergaard K. Gesant Exp Med 1929 Gruenwald described surface tension as a factor in the “resistance of neonatal lungs to aeration”. Gruenwald P. Am J Obstet Gynecol 1947 Pattle and Clements described the role of surfactant in lung stability during the respiratory cycle. Pattle R.E. Nature 1955, Clements J.A. Proc. Soc Exp Biol Med 1957 Avery and Mead discovered that surfactant deficiency was the cause of neonatal respiratory distress syndrome (RDS). Avery M.E. & Mead J. Am J Dis Child 1959 In 1972 the importance of the hydrophobic proteins was described by Clements and co-workers but successful treatment in humans did not occur until 1980. Clements J.A. Physiologist 1962
Law of Laplace: the pressure inside a bubble is inversely proportional to the radius, due to the surface tension of fluid lining. This surface is created by the air-fluid interface. Bubbles with a small radius need large pressure to keep them inflated. Bubbles with a large radius need less pressure. The effect of the Law of Laplace is more complex on alveoli because they are all interconnected, therefore if one tends to collapse it will expand neighbouring alveoli. Obeying Laplace's law smaller alveoli would tend to collapse at end expiration forcing air into the larger alveoli that over-inflate. However the film pressure generated by surfactants acts to neutralise the differences and stabilise the lung.
Surfactant is a complex substance containing phospholipids and a number of apoproteins. This essential fluid is produced by the Type II alveolar cells, and lines the alveoli and smallest bronchioles. Surfactant reduces surface tension throughout the lung, thereby contributing to its general compliance. It is also important because it stabilizes the alveoli. LaplaceХs Law tells us that the pressure within a spherical structure with surface tension, such as the alveolus, is inversely proportional to the radius of the sphere (P=4T/r for a sphere with two liquid-gas interfaces, like a soap bubble, and P=2T/r for a sphere with one liquid-gas interface, like an alveolus: P=pressure, T=surface tension, and r=radius). That is, at a constant surface tension, small alveoli will generate bigger pressures within them than will large alveoli. Smaller alveoli would therefore be expected to empty into larger alveoli as lung volume decreases. This does not occur, however, because surfactant differentiallyreduces surface tension, more at lower volumes and less at higher volumes, leading to alveolar stability and reducing the likelihood of alveolar collapse. Surfactant is formed relatively late in fetal life; thus premature infants born without adequate amounts experience respiratory distress and may die.
Pulmonary surfactant is a complex mixture of lipids and specific apoproteins, 80% phospholipid, 8-10% neutral lipids and 10-12% proteins. The phospholipid component consists of 60% saturated phosphatidylcholine (PC), 20% unsaturated PC and anionic phospholipids, phosphatidylglycerol (PG) and phosphatidylinosotol. The main active component is dipalmityl phosphotidylcholine (DPPC) which is responsible for reducing surface tension and maintaining alveolar stability. The protein part of the surfactant system is a small fraction of pulmonary surfactant and includes two major categories differing in structure and hydrophobicity.
Interaction of surfactant with airway inflammation in asthma. After uptake through the airway surfactant barrier (right side of figure), allergens are presented by dendritic cells (DC) to T cells (T) that release IL-2, proliferate, and differentiate into T helper 2 lymphocytes (Th2). These Th2 cells release cytokines (IL-4 and IL-5) that attract eosinophils (Eos) and stimulate IgE production by differentiated B lymphocytes (B). IgE is bound to mast cells (MC) that, upon stimulation with allergen, release mediators (such as histamine) inducing acute asthma attacks. Activated eosinophils degranulate and release toxic mediators like eosinophil cationic protein (ECP), leukotrienes (LT), and transforming growth factor-β (TGF-β) that induce epithelial damage and chronic airway inflammation. ECP is shown in bold because ECP, but not LT or TGF-β, has been shown to cause surfactant dysfunction (unpublished data). The various effects of surfactant proteins SP-A, SP-B, SP-C and SP-D are indicated. SP-A and SP-D are shown in bold to emphasize the importance of these surfactant molecules as immunomodulators in asthma. Mechanisms of stimulation, activation, induction, or release are symbolized by arrows whereas inhibition, decrease, or down-regulation are symbolized by lines terminated by =. ? is used to indicate that the effects of SP-A/SP-D are presently unclear. PL = phospholipid.
A number of indices of foetal lung maturity based on the determination of surfactant constituents in the amniotic fluid have been proposed. Amniotic fluid contains phospholipids, including phosphatidylcholine (lecithin), sphingomyelin, phosphatidylinositol and phosphatidylglyerol (PG), some enzymes of the pathways of phospholipid synthesis, lamellar bodies, and lung specific apoproteins. The amount of these substances in amniotic fluid changes towards the end of gestation in a manner related to foetal lung maturity. Determination of the lecithin to sphingomyelin (L/S) ratio is by far the most widely used and accepted method. However, there is still controversy regarding the high incidence of false immature values, and the increased incidence of false mature values (from 1 to 15%) especially in pregnancies complicated by diabetes mellitus; an immature L/S ratio may predict respiratory distress syndrome (RDS) only in about 50% of cases. The incidence of false immature L/S ratio as well as other amniotic fluid tests depends upon patient variability, method employed, threshold taken for differentiating a normal from an abnormal condition, and on the fact that only few authors report their results in terms of sensitivity and specificity. Where laboratory facilities are minimal, it is advisable to perform the shake test or to measure the optical density of amniotic fluid. However, when these tests indicate immaturity, additional tests, such as determination of the L/S ratio or the lung profile (including PG), must be performed.
