Cell Biology Flashcards
How does alveolar positioning maximise airway SA?
fold round onto the large airways to give economy of space
At which generation do the alveolar sacs end ?
generation 23
the cross sectional area of the lung increases peripherally
At which generation are the terminal bronchioles located?
5-16
What comprises the lung lining liquid?
surfactant - phospholipid rich substance to prevent lung collapse and stick together
secretions - lung defense
Why do lungs collapse in premature birth?
type 2 cells that make surfactant do not appear till late in gestation (after 24wks)
What 3 things does COPD consist of?
emphysema
bronchitis
small airways disease
advanced COPD - large holes, loss of elasticity
Function of epithelium?
- continuous barrier
- secretions to aid mucociliary clearance of debris, pathogens, protection, maintain reduced surface tension
- metabolise foreign and host derived compounds
- release mediators
- repair/regeneration
Pathology of COPD?
increase goblet cell numbers (hyperplasia) can become cancerous
increased mucus secretion
fewer cilia
cannot clear mucous efficiently
Goblet cells?
- throughout lungs (20% epithelium) but more in large than small airways
- make and secrete mucus
- number doubles in smokers, secretions increase and are more viscoelastic –> harbour microorganisms so increase chance of infection (bronchitis)
Cilia?
60-80% of epithelium in smokers: - severely depleted - asynchronous beat - found in bronchioles (further down airways) where they block smaller airways - cannot transport thicker mucus - infection (bronchitis) and obstruction
What holds an intact airway open?
What happens in COPD?
intact alveolar wall with elastic tissue
- broken alveolar attachments so inspiration will not inflate alveoli
- abnormal epithelium, excess mucus, hypertrophy of submucosal glands
- fibrosis in attempt to repair tissue but irreversible damage
- inflammatory cells accumulate
How does increased small airways disease influence lung function?
exacerbates it
What classifies small airways?
less than 2mm and no cartilaginous material
What enriches terminal respiratory bronchioles?
club cell - non ciliated secretory bronchiolar epithelial cell
- in small airways
- secretory granules
- xenobiotic metabolism (break down enzymes and organisms) (detoxification)
- secretory
- repair cells
Cilia in smaller airways?
shorter
What influences COPD onset?
genetics and environment (smoking)
What 2 cells make up alveolar surface?
Type II epithelial cell
Type I cell (95% of surface)
ratio 1:2
Function of Type I cell?
- thin, stretched out so covers more of surface (95%)
- facilitate gas exchange and solute transport across alveolar epithelium
- strong
Function of Type II cell?
- small secretory cuboidal cell that makes surfactant to prevent alveolar collapse on expiration
- contain lamellar bosies that store surfactant before release onto air-liquid interface
- cells in corners of alveoli, embedded in interstitium
- repair/progenitor cells for T1 also (stem cells)
- detoxification
Are there ciliated cells in alveoli?
no
macrophages compensate by engulfing pathogens/particles and migrating via mucociliary escalator / lymphatics
What are stromal cells (myofibroblasts)?
- make ECM that cells sit on
- collage and elastin to give elasticity and compliance
- divide to repair
What is wrong with overdrive of stromal cell proliferation?
lead to interstitial fibrosis
- lungs solid
- cannot breathe any more
Histopathology of emphysema?
- alpha 1 antitrypsin deficiency WITH smoking are more prone to emphysema because A1A made in liver inhibits neutrophil elastase made by neutrophils –> deficiency destroys functioning of lung
- fibroblasts attempt to repair but lead to fibrotic rigid regions
What drives gas exchange in alveoli?
short diffusion distance
under 1 micrometre thick
What happens to repair in alveolar fibrosis?
- type II cells dont differentiate to type I cells
- gas exchange severely affected
- fibroblasts proliferate to myofibroblasts which cause Type II cells to release factors that stimulate fibroblast proliferation to create ECM and to prevent Type II cells from converting to Type I
Role of stromal cell (fibroblasts) in lung repair and fibrosis?
- epithelial cells try to repair and differentiate to Type I cells 2. abnormal repair - due to elevated growth factors
Type I cell death, Type 2 cells not converted and proliferated
–> reduced gas exchange
3.fibroblasts proliferate to give lots of connective tissue
What can Type II cells do?
become myofibroblasts or Type I cells or apoptose
if become myofibroblast (undesirable)
What do cigarettes do ?
Increased apoptosis/necrosis of epithelium
Block repair processes - no myofibroblasts formed, no transdifferentiation to Type I
What are functions of secretory epithelial cells?
- secrete protective layer to trap debris/pathogens (surfactant, mucus)
- make antioxidants (glutathione, superoxide dismutase)
- synthesis and secrete antiproteinases (SLPI - superior leukoproteinase inhibitor (SLP1)
- release lysozyme
- carry out xenobiotic mechanism to detoxify foreign compounds such as carcinogens
- contain cytochrome P450
What happens after cigarette smoke exposure?
- increased number of inflammatory cells in lung (macrophages and neutrophils) up to 10 fold
FUNCTION phagocytosis antimicrobial defence make antioxidants xenobiotic metabolism
What if more neutrophils than macrophages?
if lung infection has reached alveoli
mainly macrophages (90%) neutrophils up to 10% but can be up to 30% (smoker with infection)
70: 30 macrophage to neutrophil ratio in non smokers and reverse in COPD
- lots of neutrophils as bacteria not being removed by cilia
What enzymes do neutrophils and macrophages produce?
serine proteinases (neutrophil elastase) and mettalloproteinases (MMP9, Zn/metal at reactive site)
- Excess of these and lack of antiproteinase can digest lung and lead to holes
- activate other proteinases and inactivate antiproteinase
- activate cytokines/chemokines/proinflammatory mediators
What antimicrobial substance do macrophages/neutrophils produce?
oxidants
interact with proteins and lipids
make highly reactive peroxides
inactivate alpha 1 antitrypsin
fragment connective tissue
What do macrophages secrete to regulate their function?
secrete mediators (chemoattractants/cytokines like IL8) to attract more inflammatory cells in infection/after toxicant/microbial deposition
also make GFs to help repair of tissue
What do club cells, type II cells and macrophages contain?
phase 1 and 2 enzymes needed for xenobiotic metabolism
What happens if too much active carcinogen?
active carcinogen made by Phase 1 enzyme in lung cells
–> this in normal metabolism is mate water soluble and excreted by Phase 2 enzymes
but if overloaded with carcinogen/inactive enzyme –> no metabolism –> DNA binding, adduct forms, no repair, mutation
What can be seen as high in smokers?
adducts
precursor to lung cancer
DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could be the start of a cancerous cell, or carcinogenesis.
