Respiratory Diseases 1 Flashcards

1
Q

What is a common trigger for the development of chronic lung diseases?

A

Environment

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2
Q

What is the basic anatomy of the lungs?

(4 marks)

A
  • 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
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3
Q

What are the conducting and respiratory zones?

(2 marks)

A
  • Conducting zone: where air is drawn and conducted
  • Respiratory zone: where air is exchanged
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4
Q

What are the different lung compartments?

(4 marks)

A
  • Large airways
  • Small airways (no cartilage so easier to collapse & phenotypes occur here)
  • Terminal bronchioles
  • Alveoli (phenotype mutations occur here)
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5
Q

What is the function of the airway epithelium?

(3 marks)

A
  • Protective barrier function
  • Clearing of inhaled pathgoens and irritants
  • Anti-microbila defence, recruitment of immune cells
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6
Q

What are basal cells and what do they do?

(2 marks)

A
  • Stem cells of airway in injury
  • Repair and differentiate into ciliated secretory cells
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7
Q

What are ciliated cells and what do they do?

A
  • Airway clearance (removal of debris and pathogen out of airways)
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8
Q

What are goblet cells and what do they do?

(2 marks)

A
  • Secretory cells (SCGB1A1 pos+)
  • Secrete mucus can trap pathogens
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9
Q

What are different ways of studying epithelial function in the lab?

(8 marks)

A
  1. Submerged culture: isolate cells from different locations and grow in monolayer (simplest)
  2. 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
  3. Organoid cultures: combine different cell types. Take stem cells and grow in matrigel which will form round balls that’ll differentiate and grow
  4. 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
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10
Q

What are teh 3D models used for epithelial cell differentiation?

(3 marks)

A
  • 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)
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11
Q

What is Forced vital capacity (FVC)?

A

Total air volume you can exhale in one breath

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12
Q

What is Forced expiratory volume (FEV1)?

A
  • Most amount of air volume you can breathe out in one breath
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13
Q

What is considered an obstructive ratio?

A
  • FEV1/FVC ratio <0.7
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14
Q

What is chronic obstructive pulmonary disease (COPD)?

A

Heterogenic disease, normally affects older people

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15
Q

What are some of the environmental triggers to the development of COPD?

A
  • Smoking, air pollution, bio-fuel
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16
Q

What are some host factors that may increase the risk of COPD?

(2 marks)

A
  • Epigenetic changes
  • Size of lungs - small
17
Q

What is airway remodelling?

(4 marks)

A
  • Air pathway very narrow
  • Increase mucus secretion
  • Small airway fibrosis
  • Chronic inflammation
18
Q

What is alveolar destruction? (4 marks)

A
  • Emphysema= damage to alveolar walls, leads to collapse and air trapping
  • Chronic inflammation
  • Causes airflow limitationa and obstruction
19
Q

What are the phenotypes of COPD?

(5 marks)

A
  • Airway remodelling
  • Alveolar destruction
  • Stem cell loss
  • Impaired repair capacity
  • Airway and alveolar stem cells turning into fibroblasts
20
Q

What are the clincal phenotypes of COPD?

(4 markers)

A
  • 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
21
Q

What is squamous metaplasia?

A

Epithelium nto efficiently able to clear anything

22
Q

What is goblet cell metaplasia?

A

In small airway due to wrong differentation of basal cells

Goblet cells in the wrong place

23
Q

What is the mechanism of COPD?

(8 marks)

A
  • 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)
24
Q

What is cellular sensence?

(2 marks)

A
  • Irreversible cell cycle - arrest is driven by variety of mechanisms
  • Could be telomere shortening or other forms of genetic stress or mitogens/ inflammatory cytokines
25
Q

What effects does oxidative stress as a key driver have on COPD?

(4 marks)

A
  • Telomere shortening
  • DNA damage
  • Mitochondrial dysfunction
  • Stem cell exhaustion and senscence
26
Q

What do senecent cells secrete?

A

Inflammatory mediators and proteases

27
Q

Why are old people more likely to be affected by COPD?

(4 marks)

A
  • 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
28
Q

How is COPD diagnosed?

(4 marks)

A
  • 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)
29
Q
A