5- Cell Biology Of The Lungs

Question 1

How many generations of dichotomous branching are there and which make up the 3 sections of the airways

Answer 1

23
0-16 conducting
17-19 transitional
20-23 respiratory

Question 2

What fraction of epithelial cells are goblet cells

Answer 2

1/5

Question 3

What does mucous contain

Answer 3

Mucin proteins, proteoglycans and glycosaminoglycans released
from goblet cells and seromucous glands. Give mucus viscoelasticity
• Serum-derive proteins, such as albumin and alpha 1-antitrypsin
also called alpha 1-proteinase inhibitor, an inhibitor of polymorphonuclear neutrophil proteases. Combats microorganism and phagocyte proteases.
• Antiproteases synthesised by epithelial cells r. Combats microorganism and phagocyte proteases.
• Antioxidants from the blood and synthesised by epithelial cells and phagocytes. Combats inhaled oxidants e.g. cigarette smoke, ozone. Also counteracts excessive oxidants released by activated phagocytes.

Question 4

What happens to goblet cells in smokers

Answer 4

Goblet cell number at least doubles (hyperplasia)
• Secretions increase in quantity
• Secretions are thicker

Question 5

What happens to ciliates cells in smokers

Answer 5

Ciliated cells are severely depleted
• Cilia beat asynchronously
• Ciliated cells found in bronchioles (even though reduced in airways)
• Cilia unable to transport thickened mucus - reduced mucus
clearance

Question 6

What are 2 features of the small airways

Answer 6

<2 mm in diameter Not cartilagenous

Question 7

What are Clara cells

Answer 7

Clara Cells = non-ciliated secretory epithelial cells found in large, central, and small airways and bronchi and bronchioles
A major role is XENOBIOTIC METABOLISM
Contain phase 1 and 2 enzymes

Question 8

Describe type 2 pneumocytes

Answer 8

Contain lamellar bodies that store surfactant prior to release onto the air-liquid interface
Synthesise and secrete antiproteases
Positioned in the corners of the alveoli and are embedded in the interstitium with the apical membranes facing the air
Type II cells are very close to capillaries
Type II cells are a precursor for alveolar epithelial type I cells - they divide and differentiate to replace damaged type I cells

Question 9

Decreased type 1 pneumocytes

Answer 9

95% of alveolar surface

Thin and strong

Question 10

What is the ration of t2:t1

Answer 10

2:1

Question 11

Describe alveolar macrophages

Answer 11

Form about 70% of total phagocytic cells in a normal lung
• Macrophages INCREASE 5-10 fold in smokers lungs
Send ‘messages’ to blood/lymphatic system to sequester other inflammatory cells (e.g. neutrophils/lymphocytes) to lungs during infection or as a result of toxicant deposition/inhalation

Question 12

Polymorphonuclear Neutrophils:

Answer 12

found throughout the airways
• Usually only about 5% of lower respiratory tract phagocytes
• INCREASE significantly in number (5-10 fold) and proportionally (up to 30% of
total phagocytes) in smokers and more so during infection

Question 13

Describe the histopathology of emphysema

Answer 13

Infection –> Chronic Damage (T1 cell death) –> Alveolar Fibrosis (repair mechanism)
Increased type II epithelial cells
Increased number of fibroblasts - make a lot of connective tissue (fibrosis)

Question 14

Summarise the effects of smoking

Answer 14

Blocks proliferation and differentiation of Type II cells into Type I cells - and
stimulates apoptosis and necrosis of Type I and Type II cells
Also blocks communication between TII cells and fibroblasts - therefore
blocking repair mechanisms
• INCREASES 10-FOLD NUMBER OF MACROPHAGES AND NEUTROPHILS
Secrete serine proteases (e.g. neutrophil elastase) and metalloproteases (e.g. MMP9), which activate other proteinases and activate cytokines/ chemokines and other pro-inflammatory mediators therefore increasing the number of inflammatory molecules within alveoli —> alveolar inflammation
Also release antimicrobial oxidants - which generate highly reactive peroxides, interacting with proteins and lipids fragmenting connective tissue –> damage
Macrophages also secrete mediators - growth factors + proteases trigger growth and repair by other cells
• Contains Procarcinogens which are activated by phase I enzymes
In normal metabolism, phase II enzymes make these water soluble so that they can be metabolised and excreted
Smoking overloads the pathway, and may inactivate the enzyme, therefore the carcinogen may undergo DNA binding, adduct formation, no repair and mutation