Lecture 10 - CF: Respiratory System Flashcards Preview

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Flashcards in Lecture 10 - CF: Respiratory System Deck (65):
1

Describe the anatomy of the respiratory system

Series of branching tubes:
• Upper airways
• Trachea
• Bronchi
• Bronchioles
• Terminal bronchioles
• Respiratory bronchioles
• Alveolar ducts
• Alveoli

2

What is the difference between the conducting and respiratory zones?

Conducting: mucosa lined, no gas exchange
Respiratory: simple squamous epithelium for gas exchange

3

What are the phases of lung development?

1. Embryonic: lung bud appears, out pouching from foregut

2. Pseudoglandular: branching of airways up to terminal bronchioles

3. Canalicular: development of acinar region & type I and II pneumocytes

4. Sacular / alveolar:
• sacules form into alveolar ducts
• decrease in interstitial tissue, septation
• alveoli start to develop

4

What is the tissue origin of the lungs?

Endoderm

5

What is the acinus?
Of what is it composed?

This is the gas exchange region of the lung

Composed of:
• respiratory bronchioles
• alveolar ducts
• alveolar sacs
• alveoli

6

What is septation?

Septa form between alveoli to form more alveoli

7

What are some functions of the lungs?

• Gas exchange
• Defence
• Acid-base balance
• Metabolic
• Heat exchange
• Water balance
• Phonation

8

What are the defences in the lung?

Upper:
• cough reflex
• sneezing
• mucociliary escalator
• turbinates, filter
Lower:
• surfactant
• IgA
• complement
• alveolar macrophages

9

What is ASL and what is it composed of?

Airway surface liquid:
• periciliary layer
• mucous gel layer

10

Describe the function of the mucociliary escalator

ASL present on cells in lumen
Cilia on apical surface beat 12-15 times per second

11

Describe gas exchange in the lungs

• Takes place at the level of alveoli
• Alveoli filled with air upon inspiration
• Gas diffuses in solution across the single celled wall of the alveolus into the capillary
• Basement membrane between alveolus and capillary

12

What is the measurement of 'Flow'

Volume / time (of air)

13

Which parameters do we measure to determine lung function?

• Volume
• Flow
• Pressure

14

What are the various lung volumes and capacities of the lungs?

Total lung capacity
Vital capacity
Tidal volume
Residual volume
Expiratory reserve volume
Inspiratory reserve volume
Inspiratory capacity
Expiratory capacity

15

Describe how FEV and FVC are measured

1. Maximal inspiration
2. Forced expiration until residual volume
First second: FEV
Until residual volume: FVC

16

When is most of the air exhaled when performing Spirometry?

First second

17

What happens with reversible intrathoracic airway obstruction?

Air can't be exhaled as quickly

18

What are some pulmonary complications of CF?

• Poor lung function, progressive decline
• Cough and sputum production
• Dyspnoea
• Need for transplantation; death
• Respiratory failure

19

What causes lung disease in CF?

The CFTR mutation(s)

20

Which cells in the respiratory system express CFTR?

Epithelium of respiratory tract
Alveolar macrophages
Serous cells of submucosal cells
Type II pneumocytes
Neutrophils

21

What is the role of CFTR in the epithelium of the respiratory tract?
Describe what happens to this process in CF

Modulates the composition of ASL
1. Cl- secretion through CFTR
2. Na+ and H20 absorption through ENaC

In CF:
1. No Cl- secretion
2. No ENaC inhibition; increased Na+ and H2O absorption
3. Decrease in ASL volume

22

What are the sequalae of reduced ASL volume?

• Reduced ciliary beating in periciliary layer
• Decreased lubrication, adherence of mucous plaque

→ Promotes chronic infection

23

Discuss the interaction between CFTR and Bicarbonate ions

CFTR important for bicarbonate ion transport

Mutation leads to:
→ improper pH regulation of ASL (airway surface liquid)
→ inhibits antimicrobial function

24

What are the thick mucous plaques in the airways of CF patients?

Adhere to airway epithelial surface

25

Describe the anaerobic milieu

Increased oxygen consumption of epithelial cells
→ anaerobic environment

This anaerobic environment is ideal for the growth of bacteria
→ Pseudomonas aeruginosa converts to anaerobic biofilm mode of growth

26

What is the common feature of lung inflammation in individuals with CF?
Describe the effect of this

Presence of great n°'s of neutrophils, causing:
• tissue damage
• neutrophils possess large amount of oxidants and proteases that damage tissue when the cells are present in too large numbers (regurgitation, etc.)

27

Why are the lungs of individuals w/ CF under such great oxidative stress?
What is the effect of this?

Oxygen radicals from:
• air
• bacteria
• host immune response

Leads to:
• pulmonary deterioration
• bronchiectasis
• oxidation of airway proteins
• inflammation

28

What is bronchiectasis?

Dilation of part of bronchial tree, caused by muscle and elastic tissue damage

29

What causes the release of large amounts of pro-inflammatory cytokines in the lungs?

Epithelial innate and apative immune cells constantly triggered by:
• infectious agents
• ROS
• proteases

30

What is the role of NF-κB in CF?

(Nuclear factor - κB)
Transcription factor, which is dysregulated in CF
Respiratory epithelium is increasingly pro-inflammatory

31

What is ceramide, and where is it found?
What is its role in CF?

• Ceramide is a breakdown product of Sphingomyelin
Found in:
• plasma membrane
• endosomal compartments

Role in CF:
1. Triggers apoptosis & pulmonary inflammation
2. Deposition of DNA from apoptotic cells

32

What are the triggers of inflammation in the airways in CF?

• Sphingomyelin
• CFTR dysfunction
• Unfolded CFTR
• TLR signalling (from microbes)

33

Describe the role of pulmonary inflammation in CF and pathogens

The pulmonary inflammation may facilitate pathogenesis of organisms:
e.g.
• Pseudomonas stimulates lipid raft formation
• Lipid rafts contain CFTR and cave-in-1
• Lipid rafts stimulate uptake of the bacterium into epithelial cells

34

Describe the vicious cycle of pulmonary dysfunction in CF

• Mutation in CFTR gene → viscous mucous
• Viscous mucous → airway obstruction & predisposes infection
• Infection → inflammation
• Inflammation → favours thick mucous production

And the cycle continues...

35

What can infection, obstruction and inflammation of the airways lead to?

Bronchiectasis
(dilation & damage of bronchi)
• neutrophilic inflammation in and around bronchi
• enlargement of lungs

36

Which infectious agents are individuals with CF particularly susceptible to?

• Pseudomonas
• S. aureus

• Haemophilus influenza
• Mycobacteria

37

Describe what happens to lung function over the years in individuals with CF

• Slow decrease in lung function
• Measured as decreased FEV1

NB better outcomes now, as compared to 20 years ago

38

When does the lung bud first appear during development?

Day 26-28

39

What is being referred to when people say: 'lung function is 80%'?

FEV1

40

What is the normal effect of CFTR on ENaC in the lungs?

Normally inhibits ENaC, reducing the Na+ that can come into the epithelial cells

41

What are the two important antioxidants?

Glutathione
Thiocyanate

42

Discuss the interaction between CFTR and antioxidants

CFTR important in Glutathione and Thiocyanate maintenance in epithelial fluid lining

With CFTR mutation, we see increased:
• oxidative stress
• lung inflammation

43

Which bacteria commonly infect the CF lung?

• P. aeruginosa
• S. aureus
• H. influenzae

44

What is bad about P. aeruginosa infection in the body?

They form biofilms
Makes it hard for the immune system to clear
Resistant to antibiotics

45

Is CF obstructive or restrictive?

Obstructive

46

What happens to FEV1 in CF?

Decreased: not as much volume can be exhaled in the first second as predicted

47

When performing spirometry, does it take longer or shorter for a person w/ CF to empty their lungs?

Longer

48

What is the tissue origin of the lungs?

Endoderm
Out-pouching of the primitive foregut

49

When is the embryonic phase?

0-6 weeks

50

When does the epithelium of the lungs thin?

Canalicular

51

When does septation occur?

Alveoar / sacular

52

When do the lungs start to resemble the lungs in babies and adults?

Pseudoglandular

53

When do the pneumocytes start to thin?

Canalicular

54

When does the acinar region develop?

Canalicular

55

When is the pseudo glandular phase?

6-16 weeks

56

When is the sacular phase?
What is this also called?

26-36 weeks
Alveolar

57

When do the pneumocytes form?

Canalicular

58

Describe the connections between the following terms:
• respiratory bronchiole
• alveolar duct
• alveoli
• alveolar sac

Alveolar ducts are tiny ducts that connect the respiratory bronchioles to alveolar sacs, each of which contains a bunch of alveoli (the balls)

59

When do the alveoli start to develop?

Sacular / alveolar

60

When is there a decrease in interstitial tissue in development?

Sacular / alveolar

61

When is the canalicular phase?

16-26 weeks

62

How many alveoli in a baby?

1/3rd of the number present in adults

i.e. 100 million

63

Compare the surface area of the respiratory surface of the lung in babies and adults

Babies: 4 m squared
Adults: 10 m squared

64

What happens in the post-natal phase?
When is this?

Birth to unknown

Lungs continue to develop after birth, but it is unclear when it finished (at least into the teenage years)

65

List all the ways that CFTR mutation can disrupt lung function

1. Dysregulated Cl- and Na+ transport

2. Dysregulated Bicarbonate transport

3. Dysregulated antioxidants

4. Pro-inflammatory nature of CF epithelium

5. Protein accumulation

6. Anaerobic milieu

7. Oxidative stress

8. Neutrophilic inflammation