Respiratory Diseases 1 Flashcards
What is a common trigger for the development of chronic lung diseases?
Environment
What is the basic anatomy of the lungs?
(4 marks)
- Right lung has 3 lobes
- Left lung has 2 lobes
- Trachea branches into bronchoas and then into secondary artery, tertiary ⇒bronchioles
- Alveoli - peripheral part of hte lung where airways lead to
What are the conducting and respiratory zones?
(2 marks)
- Conducting zone: where air is drawn and conducted
- Respiratory zone: where air is exchanged
What are the different lung compartments?
(4 marks)
- Large airways
- Small airways (no cartilage so easier to collapse & phenotypes occur here)
- Terminal bronchioles
- Alveoli (phenotype mutations occur here)
What is the function of the airway epithelium?
(3 marks)
- Protective barrier function
- Clearing of inhaled pathgoens and irritants
- Anti-microbila defence, recruitment of immune cells
What are basal cells and what do they do?
(2 marks)
- Stem cells of airway in injury
- Repair and differentiate into ciliated secretory cells
What are ciliated cells and what do they do?
- Airway clearance (removal of debris and pathogen out of airways)
What are goblet cells and what do they do?
(2 marks)
- Secretory cells (SCGB1A1 pos+)
- Secrete mucus can trap pathogens
What are different ways of studying epithelial function in the lab?
(8 marks)
- Submerged culture: isolate cells from different locations and grow in monolayer (simplest)
- Air liquid interface: put same stem cells in & give differntation medium and expose them to air. Different compartments - cells exposed air, mucus secreting cells and basal cells at bottom exposed to medium
- Organoid cultures: combine different cell types. Take stem cells and grow in matrigel which will form round balls that’ll differentiate and grow
- Lung on chip: engineer airflow and medium channels you’ll get different cell types which will eliminate epithelium and mimic breathing. Can get disease modelling
What are teh 3D models used for epithelial cell differentiation?
(3 marks)
- Air-liquid interface: express different markers for certain cells - allows for differentiation
- Spheroids in matrigel: stain for particular cells - can view property of cells
- Co-cultures organoids: good to look at cell:cell crosstalk (fibroblasts and AEC’s)
What is Forced vital capacity (FVC)?
Total air volume you can exhale in one breath
What is Forced expiratory volume (FEV1)?
- Most amount of air volume you can breathe out in one breath
What is considered an obstructive ratio?
- FEV1/FVC ratio <0.7
What is chronic obstructive pulmonary disease (COPD)?
Heterogenic disease, normally affects older people
What are some of the environmental triggers to the development of COPD?
- Smoking, air pollution, bio-fuel
What are some host factors that may increase the risk of COPD?
(2 marks)
- Epigenetic changes
- Size of lungs - small
What is airway remodelling?
(4 marks)
- Air pathway very narrow
- Increase mucus secretion
- Small airway fibrosis
- Chronic inflammation
What is alveolar destruction? (4 marks)
- Emphysema= damage to alveolar walls, leads to collapse and air trapping
- Chronic inflammation
- Causes airflow limitationa and obstruction
What are the phenotypes of COPD?
(5 marks)
- Airway remodelling
- Alveolar destruction
- Stem cell loss
- Impaired repair capacity
- Airway and alveolar stem cells turning into fibroblasts
What are the clincal phenotypes of COPD?
(4 markers)
-
Pink puffers:
- mostly emphysema - pink skin, severly breathless, minimal cough, pursed lips, hyperinflammation of lung
-
Blue bloaters:
- mostly bronchitis - ankle swelling, overweight, chronic productive cough, wheezing
What is squamous metaplasia?
Epithelium nto efficiently able to clear anything
What is goblet cell metaplasia?
In small airway due to wrong differentation of basal cells
Goblet cells in the wrong place
What is the mechanism of COPD?
(8 marks)
- Caused by cigarette smoke and other environmental factors
- Macrophages triggered on epithelial cells
- Activation of immune system
- Fiborblasts surround are around areas that secrete a lot of ECM
- Makes matrix stiff, fibrotic area around airways rigid, leading to small airway fibrosis
- At same time recruit neutrophils to lungs
- COPD has too many proteases - start chopping off parts of ECM - excessive activtity causes emphysema
- Alpha-1-antitrypsin deficieny (pre-disposition to COPD)
What is cellular sensence?
(2 marks)
- Irreversible cell cycle - arrest is driven by variety of mechanisms
- Could be telomere shortening or other forms of genetic stress or mitogens/ inflammatory cytokines
What effects does oxidative stress as a key driver have on COPD?
(4 marks)
- Telomere shortening
- DNA damage
- Mitochondrial dysfunction
- Stem cell exhaustion and senscence
What do senecent cells secrete?
Inflammatory mediators and proteases
Why are old people more likely to be affected by COPD?
(4 marks)
- Have loss of stem cell renewal
- Inefficient differentation of cells and will be much more damaged
- Senescence cells will inflame and produce inflammatory mediators
- Causes alveolar destruction, immunosenescence, endothelial dysfunction and oncogenic changes
How is COPD diagnosed?
(4 marks)
- Spirometry measuring FVC
- Lower the FEV1 - worse COPD
- Chest CT - may help identify emphysema
- FEV1 and FVC ratio <0.7 ⇒ obstruction less than 70% air you can normally get out blown in less than 1 sec)
