lung cell biology Flashcards
common lung problems
asthma, smoking, cancer, cough, COPD, knock on effect with atherosclerosis and heart rate variability
folding round of tubules
surface area massive in small space
cross sectional area increases peripherally - 23 generations
diagram from slide 5
lung lining liquid
important surface layer of lung - secretions involved in lung defence; phospholipid-rich surfactant stops lung collapsing
COPD
bronchitis, small airways disease, emphysema
5 functions of epithelium
forms continuous barrier, produces secretions to facilitate clearance and protect undelying cells and maintain surface tension, metabolises foreign and host-derived compounds, releases mediators, triggers lung repair process
effect of COPD on human airway epithelium
increased goblet cell numbers (hyperplasia - can become cancerous) and increased mucus secretion
goblet cells
more in large, then central, then small airways, 20% of epithelial cells, synthesise and secrete mucus
smokers goblet cell
at least doubles, secretions increase and are more viscoelastic - traps microorganisms, enhancing infection risk
ciliated cells
more in large, then central, then small airways, 60-80% of epithelial cells, beat metasynchronously
smokers ciliated cells
severely depleted, beat asynchronously, found in bronchioles, unable to transport thickened mucus - obstruction of airways and bronchitis
intact alveolar walls hold airway open
in COPD, copious secretions disrupts alveolar walls and more secretions causes blockages in small airways
why does fibrosis occur
attempt to repair tissue of destroyed alveoli in small, bronchiolar airway, so no chance of repair; many inflammatory cells also present - emphysema
stenotic bronchiolar airway in COPD
no gas exchange happens distally to stenotic region as gas can’t get through - small airway disease
effect of COPD
decreased elasticity of supporting structure, plugging, inflammatory narrowing and obliteration of small airways, destruction of peribronchiolar support
club cells
secretory granules for detoxifying club cells, rich in bronchiolar regions and protect and repair/progenitor cells - 20% small airway epithelia
effect of smoking in susceptible subjects’ alveoli
emphysema - holes in alveoli
surface of lung
alveolar type 2 (sythesises and secretes surfactant; twice as many as type 1), type 1 (very thin - fascilitates gas exchange and solute transport across alveoli; cover most of surface)
what stores surfactant prior to release
lamellar bodies
type 2 cells
progenitor cells, precursor of type 1
alveoli
type 1, type 2 (like club - do detoxification in alveoli), capillary endothelium, no ciliated cells so many macrophages - phagocytic so engulf particles deposited here - migrate into lymphatics or mucocilliary transport; stroma cells (myo) fibroblasts - make ECM - give elasticity and compliance, divide to repair
emphysema
reduced/damaged alveoli
alveolar epithelial-endothelial barrier
very thin (<1um) type 1 cell wall for efficient gas exchange
alveolar fibrosis
type 2 divide to repair, don’t differentiate into type 1, so gas exchange severely affected, increased fibroblasts and collagen deposition
role of stromal cell (fibroblast) in lung repair and fibrosis
epithelia try to repair and divide; abnormal type 1 cell death and remains as type 2 cells
AT2 can become myofibroblast worsening problem
instead of apoptosis
cigarette smoke
block repair, transdifferentiation and proliferation - cell death
functions of all secretory cells (goblet, club, type II)
secrete protective lining layer to trap deposited particles –
surfactant and mucus, synthesise and release antioxidants eg glutathione, superoxide dismutase, synthesise and secrete antiproteinases – eg secretory leukoproteinase inhibitor (SLPI), release lysosyme, carry out xenobiotic metabolism (eg process and detoxify
foreign compounds such as carcinogens in cigarette smoke), contain cytochrome P450, phase I & II enzymes etc
infection in lung/smokers
more neutrophils present (than macrophages) - phagocytosis, antimicrobial defence, synthesise antioxidants, xenobiotc metabolism
neurtophils
in respiratory units, 10%, increase in smokers if infection, in airways of non-smokers, more macrophages, in smokers, more neutrophils (both increase but neutrophils much bigger increase as lots of bacteria in airways as not being cleared)
proteinases
serine and merrallo released from neutrophils and macrophages - dissolve lungs if too many; activate each other and cytokines, chemokines and pro-inflammatory mediators
oxidants from neutrophils and macrophages
generate highly reactive peroxides, interact with proteins and lipids, fragment connective tissue
macrophages secrete mediators
chemoattractants and cytokines - attract more inflammatory cells during infection or after toxicant/microbial depositionl growth factors and proteases trigger growth and repair by other cells
club, type II and macrophages
contain phase I and II enzymes; phase I convert procarcinogen to carcinogen in lung, phase II normally make them water soluble and excreted in metabolite, but if pathway overload or inactivated causes DNA binding, adduct formation and no repair so mutation
