Biochemistry of Lung surfactant Flashcards
Which law consititutes the area/depth of the lungs?
Fick’s Law
what is the function of all the ‘splitting’ in lung airways?
the volocity of air falls rapidy as it moves down into the lung
What are the two major alveolar cells?
Type 1 = all about transfer of oxygen and good connections with blood flow 95% of the alveolar cells
Type 2 = 5% secrete pulmonary surfactant - a phsopholipid protein complex which facilitates lung expansion
What do the smooth muscle cells do in the bronchi?
They control the diameter and tension of the bronchi - amount decreases deeper in the lung - involved in asthma (chronic asthma can have increased bronchial smooth muscle content) - produces cytokines - IL5 and IL13
What is the role of lung macrophages?
- Interspersed – found along length of the respiratory tract
- Particularly important for immune defense in respiratory bronchioles.
- Function through phagocytosis (e.g. soot, spots in smokers lung, clearance of cell turnover)
- Produce potent antimicrobial agents
–Reactive oxygen species
–Proteases
•Antiviral agents
–interferon
what antiviral agent is produced by lung macrophages?
interferon
What does the release of histamine, prostaglandin D2, and Leukotriene C4D4 by the mast cells lead to?
–Cause: bronchoconstriction & increased mucous production
What are the Goblet cells of the lungs?
- Present from bronchioles up
- Located in epithelium
- Function is to secrete mucous
- Density of goblet cells is increased in Cystic Fibrosis
what are the pulmonary endothelial cells?
- Environment for alveolar capillaries
- Represents the largest and most dense vascular bed in the human body – approx 140m2
- Produce vasoactive peptides e.g.Tissue Plasminogen Activator (TPA), of ACE I – ACE II, inactivation of bradykinin (vasodilator) (CONSTRICTORS)
- Controlling blood flow, fluidity and pressure & viscosity
What are the Flat Alveolar Cell?
•Type 1 = main cells found in the alveoli
Resembles a fried egg - large & thin cells, central nucleus - make up 95% of the epithelial lining of the respiratory zone
- Fusion of type 1 epithelial cells with the pulmonary endothelium
- Responsible for gas exchange. Fusion with pulmonary endothelium results in ultra-thin layer – & diffusion
- Unable to replicate= terminally differentiated - require stem cells under the influence of other mediators to differenciate into this type of alveolar cell
What are Alveolar type 2 cells?
Large alveolar cells – Type 2 pneumocytes= stem cell
- Much less numerous than Type 1 pneumocytes- which seems counterintuitive that the cell that produces both Type 1 and Type 2 cells is much less concentrated
- Have large nuclei, microvilli (secrete surfactant) & extensive mitochondria
- Site of synthesis, storage and secretion of surfactant
- Are stem cells – can replace themselves or other pulmonary cell types after injury – can replace damaged type 1 cells
What is Surfactant?
- Lines inner surface of alveoli and bronchioles
- Surfactant reduces surface tension, relative to its concentration (otherwise small aveoli would empty in to large!)
They counteract the collapsing force of the water molecules which want to congregate together
what is compliance as it relates to the lungs?
•Compliance is the ability of lungs and thorax to expand
what is hysteresis?
•Difference in volumes, ‘Hysteresis’ - is due to the air-water surface tension that occurs at the beginning of inflation
what law states that the gas pressure needed to keep equilibrium between the collapsing force of surface tension and the expanding force of gas in an alveolus of radius r ?
Law of laplace
Increasing compliance by surfactant allows for what ?
allows the lungs to inflate more easily
what happens when an alveoli begins to collapse?
•Each alveolus is surrounded by other alveoli and interconnected by connective tissue
•
•If an alveolus starts to collapse, the surrounding alveoli are stretched as their walls are pulled in the direction of the caving alveolus
•
•The distended alveoli re-coil in response and exert an expanding force on the collapsing alveolus
what is the strongest surfactant molecule in the pulmonary surfactant mixture?
The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has higher compaction capacity than the other phospholipids, because the apolar tail is less bent
what cell secretes DPPC?
Type 2 pneumocytes
phospholipid synthesis occurs one of two ways - what ways can it occur?
(i) Donation of the phosphatidic acid from cyditine diphosphate (CDP) CDP-diacylglyercol to an alcohol (either attach a CDP to the diacylglyerol)
Or
(ii) Donation of the phosphomonoester of the alcohol from CDP-alcohol to 1,2 diacylglycerol (or attach CDP to alcohol head)
what palmates are attached to the molecule surfactant?
DPPC and apolipoproteins *addition of these two molecules make it lung specific molecule - not found anywhere else in the body*
What are the four surfactant associated proteins ?
SP-A
SP-B
SP-C
SP-D
•The major surfactant associated proteins SP-A and SP–D are hydrophilic. These are known to play a crucial role in pulmonary immunity
•
•The surfactant proteins SP-B and SP–C are very hydrophobic proteins. They are closely linked to alveolar surface-tension, phospholipid packaging and organization of surfactant structure and also have recently emergent roles in host defence
What is neonatal respiratory distress syndrome?
NRDS =
- Rapid, labored breathing in newborn (sternal retraction due to partial collapse of lungs)
- Affects 1-2% of newborn infants, approx 20% of neonatal deaths due to NRDS
- Characterised by insufficient surfactant
- Incidence correlates with degree of prematurity
- the real problem in this is that the babies heart has to work very hard to move the oxygen around the body
what can we test for when we test for fetal lung maturity?
- Sampling the amount of surfactant in the amniotic fluid by amniocentesis. Several tests are available that correlate with the production of surfactant.
- Lecithin-sphingomyelin ratio- as the lung matures you have more lecithin than sphingomyelin, therefore it’s a good predictor
- the presence of phosphatidylgycerol (PG) (precursor for the surfactant) and more recently,
- the surfactant/albumin (S/A) ratio-
