Lung Surfactant and Elastic Behavior of the Lungs PDF

Lung Surfactant Elastic Behavior of the Lungs ► Elastic Behavior of the lungs is due to elastic connective tissue and alveolar surface tension. ► During Inspiration – the lungs expand. ► During Expiration – the lungs recoil [come back to the same position]. ...

Lung Surfactant Elastic Behavior of the Lungs ► Elastic Behavior of the lungs is due to elastic connective tissue and alveolar surface tension. ► During Inspiration – the lungs expand. ► During Expiration – the lungs recoil [come back to the same position].  Elastic Behavior of the Lungs What makes the lungs behave like a balloon? ► Due to two things: 1. Compliance 2. Elastic recoil What is Compliance? ► It is a change in lung volume per unit change in airway pressure. ► It is the stretchability of the lungs. ► If the lung is less compliant, it is called a ‘Stiff Lung’ [as it lacks normal stretchability]. ► Lung compliance is decreased in pulmonary fibrosis when normal lung tissue is replaced by fibrous connective tissue due to breathing of dust e.g., asbestos fiber.  Elastic Recoil ► Elastic Recoil shows how quickly the lungs rebound [come back to normal] after they have been stretched. ► Pulmonary elastic behavior depends on two factors: 1. Connective Tissue in Lungs 2. Alveolar Surface Tension Pulmonary Elastic Connective Tissue ► Connective tissue in the lungs contains a lot of elastin fiber surrounding the alveolus, which is responsible for the expansion and elastic recoil of the lung. Pulmonary Alveoli ► Destination for inspired airflow Bear in mind that inspired/expired air is rarely “fully” exchanged ► Almost 85% of the volume of inspired air remains within the respiratory tract during the next cycle of expiration/inspiration ► Region of gas exchange ► ≅ 350 million alveoli/lung (≅ 70 M2) ► “simple” squamous epithelium ► “air-blood” barrier = 1 cell thick + basement membrane + capillary endothelium  Pulmonary Alveoli ► 2 types of alveolar cells: ► Type I = squamous epithelial cells ► Type II = “surfactant” secreting cells Surfactant = mixture of lipids & proteins (SP-A, SPB & SP-C) The goal is to reduce surface tension within the alveolus (prevent alveolar collapse) Decreases the effort to breathe & keep alveolar sacs “open”  Surfactant ► Remember that the surface of the alveoli is covered with a watery fluid with very high surface tension ► Ex: The surfaces of a wet plastic bag will stick to each other ► the walls of the alveoli tend to stick together difficult to re-open the alveoli) ► Surfactant secreted by Type II alveolar cells decrease this surface tension ► Permits more effective gas exchange ► Also permits alveolar expansion/contraction with less risk of “vacuum collapse”  Surfactant and Alveolar Surface Tension The alveolus is lined by two liquids with opposing forces 1. The attractive forces [centripetal force] between the water molecules in the liquid film that lines the alveolus are responsible for surface tension. Because of this surface tension, an alveolus ► 1. Resist being stretched ► 2.Tend to be reduced in surface area or size. ► 3. Tend to recoil after being stretched.  Surfactant and Alveolar Surface Tension ► PULMONARY SURFACTANT INTERSPERSE between the water molecules in the fluid lining the alveoli ► it lowers the alveolar surface tension because the cohesive force between water molecules and adjacent pulmonary surfactant molecules is very low 1. By lowering the alveolar surface tension, pulmonary surfactant provides two important benefits 2. It increases pulmonary compliance, thereby reducing the work of inflating the lungs. 3. It reduces the lung’s tendency to recoil and thus prevents the lung from collapsing. 4. It helps stabilize the alveoli and keep them open to participate in gas exchange.  Functions of surfactant SUMMARY ► 1. It reduces the surface tension in the alveoli of the lungs and reduces the tendency of the lungs to recoil, preventing the collapsing tendency of the lungs. ► 2.Stabilization of the alveoli. ► 3. Provides defense against infection and inflammation via specific proteins. ► 4.Keeps the lungs patent and inflated following delivery after the first breath. ► 5. It increases pulmonary compliance, thus reducing the work of inflating the lung.  Composition of surfactant SUMMARY Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. ► Composition ► ~40% dipalmitoyl phosphatidylcholine (DPPC); ► ~40% other phospholipids (PC); ► ~10% surfactant proteins (SP-A, SP-B, SP-C and SP-D); ► ~10% neutral lipids (Cholesterol); ► Traces of other substances.  Composition of surfactant ► Dipalmitoylphosphatidylcholine (D PPC) is a phospholipid consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head group. ► DPPC is the main phospholipid of pulmonary surfactant, due to its amphipathic behavior and its adsorption capacity. ► However, adsorption is not optimal at human body temperature for DPPC alone, because at 37 °C it is in a gel phase. The presence of some unsaturated phospholipids and cholesterol increases the surfactant's fluidity. ► When this mixture contacts water, for example, it accumulates at the water-air interface and forms a thin superficial pellicle of surfactant.  Composition of surfactant Proteins make up the remaining 10% of the surfactant. Half of this 10% is plasma proteins but the rest is formed by the apolipoproteins, surfactant proteins SP-A, SP-B, SP-C, and SP-D. The apolipoproteins are produced by the secretory pathway in type II cells. SP-A and SP-D are collectins. The structural components and organization of surfactant Collectins are proteins that protein A (SP-A). A: SP-A belongs to the collectin family and consists of a have a collagen domain fused collagen domain (red), a COOH-terminal carbohydrate recognition domain (CRD; yellow), and a cysteine-rich to a lectin domain. They confer NH2-terminal domain (N-term; blue). Three monomer innate immunity as they have subunits of SP-A form a trimer. carbohydrate recognition B: 6 trimers assemble into the mature SP-A protein, shown as an octadecamer or "flower bouquet." domains that allow them to coat bacteria and viruses promoting phagocytosis by macrophages..  Composition of surfactant SP-B and SP-C are hydrophobic membrane proteins that increase the rate at which surfactant spreads over the surface. SP-B and SP-C are required for the proper biophysical function of the lung. Humans born with a Lipid–protein interactions in the mechanical stabilization of alveoli during congenital absence of breathing cycles. Surfactant proteins SP-B and SP-C facilitate surfactant dynamics by regulating the mechanical properties of surfactant membranes the SP-B experience and films through direct interaction with fluid-like lipids intractable respiratory failure whereas those born lacking SP-C tend to develop progressive interstitial pneumonitis.  Production of surfactant ► Surfactant production in humans begins in type II cells during the alveolar sac stage of lung development. ► Type II cells synthesize and assemble the lipid and protein components into complexes that are stored in lamellar bodies until secreted into the alveolar Biosynthesis of pulmonary surfactant airspaces. Synthesis of the protein and phospholipid components of the surfactant may proceed via separate pathways (green lines). SP-B and SP-C traffic through the Golgi and late endosome/multivesicular body (MVB) to the lamellar body.  Production of surfactant ► Lamellar bodies are specialized lipid storage or secretory organelles that can be surrounded by a membrane and have a core composed of multilamellar membranes. ► These lamellar bodies are secreted by exocytosis into the alveolar lining fluid, where they are converted into tubular myelin. Life cycle of pulmonary surfactant. Surfactant is synthesized in the endoplasmic reticulum (ER), processed through the Golgi (G) and assembled in lamellar bodies (LB). LB are secreted into the alveolar subphase, where they are converted to tubular myelin (TM). TM gives rise to the surface film/monolayer (ML). With repeated contraction, the film yields unilamellar small aggregates (SA), which are taken up by the type II cells for degradation and recycling.  Tubular myelin The phospholipid-rich contents associate with surfactant proteins, especially SP-A, and assemble into a lung-specific structure called tubular myelin, which acts as a reservoir Tubular myelin. Surfactant phospholipids secreted into of surfactant during the alveolar space form lattice-like arrays of intersecting alveolar respiration and membranes called tubular myelin (a). Tubular myelin formation is dependent on SP-A (b) enhances the insertion of lipids into the air-liquid interface..  Production of surfactant ► Lamellar bodies appear in the cytoplasm at about 20 weeks gestation. ► Full term infants are estimated to have an alveolar storage pool of approximately 100 mg/kg of surfactant, while preterm infants have an estimated 4–5 mg/kg at birth. ► Alveolar surfactant has a half-life of 5 to 10 hours once secreted. It can be both broken down by macrophages and/or reabsorbed into the lamellar structures of type II pneumocytes. ► Up to 90% of surfactant DPPC (dipalmitoylphosphatidylcholine) is recycled from the alveolar space back into the type II pneumocyte. The other 10% is taken up by alveolar macrophages and digested.  Respiratory distress syndrome (RDS) of newborn ► Life-threatening respiratory disorder in newborn preterm babies Cause: deficiency of surfactant. ► Higher in caesarian section delivery compared to vaginal delivery ► Vaginal delivery causes stress at birth –producing cortisol [stress hormone]=Cortisol enhances surfactant production in premature lungs. ► Surface tension in the lung is high and filled with fluid, as the result lung collapse. ► Surfactant is not available to reduce the surface tension of the lung during the first cry at birth. ► First cry at birth is necessary to inflate the lungs in those with normal surfactant. ► Therapy 1. Cortisol administration to pregnant mothers at risk of preterm delivery. 2. Surfactant treatment for premature baby.  Pulmonary surfactants used in medicine Pulmonary surfactant is used as a medication to treat and prevent respiratory distress syndrome in newborn babies. Pulmonary surfactant preparations consist of phospholipids (mainly DPPC) combined with spreading agents such as SP-B and SP-C. Synthetic pulmonary surfactants: ► Colfosceril palmitate (Exosurf) – a mixture of DPPC with hexadecanol and tyloxapol added as spreading agents ► Pumactant – a mixture of DPPC and PG ► Lucinactant composed of DPPC, palmitoyl-oleoyl phosphatidylglycerol, and palmitic acid ► Lucinactant is a liquid medication that contains DPPC and palmitic acid. Animal-derived surfactants: ► Beractant (Survanta) – extracted from minced cow lung with additional DPPC, palmitic acid and tripalmitin. ► Calfactant (Infasurf) – extracted from calf lung lavage fluid. ► Poractant alfa (Curosurf) – extracted from material derived from minced pig lung. ► Surfactant TA (Surfacten) – derived from cows. ► Bovactant SF-RI (Alveofact) – extracted from cow lung lavage fluid.  NITRIC OXIDE NO is a gas with no known cellular storage mechanism. NO is the lowest molecular weight human cell product. NO is synthesized from arginine by the enzyme NO synthases - NOS.  NITRIC OXIDE SYNTHASE The NOS requires tetrahydrobiopterin, calmodulin, heme, flavins, NADPH  NOS There are three major isoforms of NOS: ► (a) neuronal NOS (nNOS) produced by neurons, ► (b) endothelial NOS (eNOS) expressed mainly endothelial cells, ► (c) inducible NOS (iNOS) induced in immune cells, astrocytes, microglia, and neurons.  NOS in lungs All three isoforms of NOS are expressed in different cells of the human lung. Specifically, NOS I is in inhibitory non-adrenergic NO gas inhalation ► NO can be used therapeutically and results in reduced pulmonary artery pressure. ► Improved perfusion of ventilated areas of the lung.