5. Lung Cell Biology Flashcards
How many generations of gas exchange units are there?
23
How does the cross sectional area of the lung increase?
Peripherally
What is the role of the epithelium?
Continuous barrier - isolates external environment from host
Produces secretions for clearance via mucociliary escalator and to protect underlying cells.
Metabolises foreign and host-derived compounds
Releases mediators
Triggers lung repair processess
Where are goblet cells present?
Large, central and small airways
What is proportion of epithelial cells are goblet cells?
1/5
Function of goblet cells?
Secrete and synthesis mucus
What does mucus contain?
Mucin proteins, proteoglycan, glycosaminoglycans, serum derived proteins, antiproteases and antioxidants
What does mucin proteins, proteoglycan and glycosaminoglycans give to the mucus?
viscoelasticity
What are 2 serum derived proteins?
Albumin, alpha 1-antitrypsin (inhibits polymorphonuclear neutrophil proteases)
What are antioxidants?
From the blood and synthesised by epithelial cells and phagocytes, they counteract oxidants released by activated phagocytes
In smokers what is the number of goblet cells?
This goblet cell number doubles
In smokers how do the secretions of goblet cells change?
Secretions increase in quantity and are thicker
Where are ciliated cells present?
Large, central and small airways
What is proportion of epithelial cells are ciliated cells?
80%
What type of beating do cilia have?
metachronous beating
What is the function of the cilia?
Tips of the cilia are in the sol phase of mucus and pushes the mucus towards the epiglottis
Describe the structure of mucus in terms of phase?
The part of the mucus touching the epithelial cells are in the sol phase. The part in contact with the air is in the gel phase
In smokers the cilia are:
1) severely depleted
2) beat asynchronously
3) found in bronchioles
4) unable to transport thickened mucus - reduced clearance
What are the size of small airways?
<2mm in diameter
Are small airways cartilagenous?
no
How does COPD affect small airways?
Mucus becomes trapped, narrowing the airway. The airway is then broken down by enzymes and inflammatory cells reducing peripheral gas exhange
What are clara cells?
Non-ciliated secretory epithelial cells found in large, central and small airways and bronchi and bronchioles
What type of airways are Clara cells found?
Conducting and transitional airways but increase proportionally distally
What is major role of Clara cells?
Xenobiotic metabolism
What is xenobiotic metaboism
Metabolism of foreign compounds deposited by inhalation
What enzymes do Clara cells contain?
Phase I, phase II, antiproteases and lysozyme
What is the function of phase I enzymes?
Metabolise foreign compounds so that phase II enzymes can react to neutralise the toxic agent
Give an example of phase I enzymes
Cytochrome p450 oxidases
What is a negative effect of phase I enzymes?
They often activate precarcinogen to a carcinogen
Give an example of Phase II enzymes
glutathionine S-transferase
COPD =
bronchitis + emphysema + small airways disease
In smokers describe the alveoli
Holes + large = reduced surface area for gas exhchange
Why does smoking cause the loss of in alveoli?
Loss of elastic tissue therefore expansion during breathing is reduced
What are the types of epithelial cells are in alveolar walls?
Type I
Type II
Which type of epithelial cell is more susceptible to damage?
Type II
Which type of epithelial cell is damaged more often?
Type I
Where are type II epithelial cells found?
alveoli
What is the function of type II epithelial cells?
Secrete surfactant which is phospholipid rich preventing lung collapse on expiration. They also synthesise and secrete antiproteases. Repair cells
Where are type II epithelial cells positioned?
On the corner of the alveoli and are embedded in the interstitium with the apical membrane facing the air
What type of cells are precursors to alveolar epithelial type I cells?
Type II cells
What is the ratio of epithelial cells in an alveolar unit?
TII:TI
2:1
What is the function of Type I epithelial cells?
Thin - to allow gaseous exchange
Cover 95% of alveolar surface
What does an alveolar unit consist of?
Type I cells Type II cells Stromal fibroblasts Alveolar macrophages Capillary endothelium
What is function of stromal fibroblasts?
Make extracellular matrix
Make collagen and elastin
Divide to repair
Where is the capillary endothelium situated?
In close proximity to alveolus to reduce diffusion distance
What is the function of alveolar macrophages?
1) Signal to inflammatory cells during infection
2) Secrete proteases
3) Generate oxidants during phagocytosis and when activated
4) Generate antioxidants to neutralise oxidative molecules
5) Contain enzyme to metabolise toxicants
What percentage of total phagocytic cells in a normal lung are alveolar macrophages?
70%
What percentage of lower respiratory tract phagocytes are polymophonuclear neutrophils?
5%
How many fold increase is the number of polymorphonuclear neutrophils and alveolar macrophages in smokers?
5-10 fold increase
What do polymophonuclear neutrophils store?
Proteases in granules
What do polymorphonuclear neutrophils release during activation?
Oxidative molcules = hydroxyl anions
Where are a large proportion of polymorphonuclear neutrophils located?
conducting/large airways
What occurs during infection - emphysema?
Infection Chronic damage (T1 cell death) Alveolar fibrosis (repair)
What happens during alveolar fibrosis?
Increased type II epithelial cells
Increased fibroblasts
What is function of fibroblasts?
To produce connective tissue and collagen
What determines whether the repair mechanisms in the alveoli occur normally or abnormally?
Communication between the type II epithelial cells and the fibroblasts
What happens in normal repair?
Type I cells die causing growth factor release which increases type II cells
What happens in abnormal repair?
There is an excess of tissue breakdown resulting in high levels of growth factor. This cause a fibrotic effect causing irreversible damage
What happens in a fibrotic effect?
Increased type II cells, fibroblasts and connective tissue synthesis in interstitial space
How does smoking affect the epithelial cells?
It blocks the proliferation of type II cells and type I cells.
Stimulates apoptosis and necrosis between Type I and II cels
Blocks communication between Type II and fibroblasts, blocking repair
How does smoking affect macrophages and neutrophils?
It increases them by 10 fold
What is the macrophage:neutrophil ratio in a non smoker?
70:30
What is the macrophage:neutrophil ratio in a COPD patient?
30:70
How do macrophages and neutrophils cause alveolar inflammation?
Secrete serine proteases and metalloproteases which activate other proteinases, cytokines, chemokines and overall increasing the number of inflammatory molecules within the alveoli
What effects does antimicrobial oxidant have?
They generate highly reactive peroxides which fragment connective tissue
What do peroxides interact with?
Lipids and proteins
What does smoking contain which are activated by phase I enzymes?
procarcinogens
What are procarcinogens activated by?
phase I enzymes
In normal metabolism what is the function of phase II enzymes?
They make active compounds/carcinogen water soluble
What is the point of making active compounds soluble?
So they can be metabolised and excreted
How does smoking affect phase II enzymes?
They may inactivate the enzyme
Overload the pathway so that there are not enough enzymes to cope with the amount of carcinogen
