Disease of the Respiratory System

Question 1

Obstruction lung disease is: eg.

Answer 1

Conditions that make it hard to exhale all the air from the lung and harder to breathe, especially during increased activity.
Eg: COPD, Asthma and Cystic Fibrosis

Question 2

Restrictive lung disease is: eg.

Answer 2

Conditions that have a much more difficult time filling their lung with air. The lung is restricted from fully expanding.
Eg: Pulmonary Fibrosis

Question 3

COPD classification:

Answer 3

1. Chronic bronchitis (blue bloater patient)

2. Emphysema (pink puffer patient)

Question 4

Chronic bronchitis main features:

Answer 4

• Excessive mucus production due to enlargement of submucosal glands, causing obstruction of the airways.
• Hypertrophy of the submucosal gland
• Goblet cell Hyperplasia (AB-PAS–> strains for mucus)

Question 5

Emphysema main features:

Answer 5

• Holes in the lung

- Destruction of the alveolar walls

Question 6

Acinus, centriacinar and panacinar:

Answer 6

Acinus: include respiratory bronchioles, alveolar ducts and alveoli.
Centriacinar: Affect respiratory bronchioles (related with cigarette smoking)
Panacinar: Affect Alveoli/ducts. (related with AAT deficiency)

Question 7

Alpha-1-antitrypsin (AAT) deficiency:

Answer 7

• COPD or smoking increases neutrophils in lungs and release netrophil elastase (NE) which degrade the lung.
• AAT inhibits neutrophil elastase (NE), but if there is an deficiency in AAT, NE is not inhibited so there is degradation of the lung.

Question 8

Neutrophil elastase (NE) is

Answer 8

an elastolytic enzyme degrading the lun architecture.

Question 9

Spirometry: assessment of airflow limitation

Answer 9

• A post-bronchodilator FEV1/FVC < 0.70 confirms and indicated an obstructive airway disease.
• Look at the force and total amount of air expired from lung.

Question 10

Complex Pathogenesis of COPD, but main features:

Answer 10

• Protease/anti-protease imbalance: increase protease (contribute to the alveolar wall destruction and cucuous hypersecretion), inhibition of antiproteases that combat those.
• Oxidative Stress: Activate and recruit anti-inflammatory cells which release ROS.
• Lung Inflammation: imflammatory response/chronic inflammation.
• Classified as a Th1/Th17 disease because of the T cell profile present.
• Matrix metalloproteinase (MMP) released which contribute to the overall emphysema components and lung tissues destruction.

Question 11

Asthma is

Answer 11

• Chronic inflammation with variable expiratory airflow limitation that is reversible.
• Is a Th2-dominant inflammatory disease

Question 12

Atopic asthma:

Answer 12

Allergic, extrinsic (most commun) Pollen, animal dander, dustmites.

Question 13

Non-atopic asthma:

Answer 13

Non-allergenic, intrinsic, triggers by virus, polluant, chemicals, cleaning agents…

Question 14

Clinical feature of Asthma:

Answer 14

Airway Hyperresponsiveness (AHR) is a exaggerated response to a bronchoconstrictor eg. Exercise, cold air, or Methacholine.

Question 15

Methacholine challenge use to calculate the Provocative Concentration of 20% (PC20):

Answer 15

NORMAL: If PC20 > 16mg/ml
ASTHMA: PC20 < 8mg/ml

Question 16

Asthma pathology characteristics:

Answer 16

• Inflammation (presence of eosinophils)
• Airway remodeling (subepithelial thickness increased, increased muscle, mucous, presence of eosinophils and smooth muscle hyperplasia)
• Bronchoconstriction (Smooth muscle hyperplasia)

Question 17

Abnormal structural change in Asthma: (4 components)

Answer 17

1. Increased nomber of blood vessels
2. Subepithelial fibrosis (collagen deposition)
3. Smooth muscle hyperplasia and hypertrophy
4. Increased volume of submucosal glands

Question 18

Asthma is a Th2-dominant inflammatory disease, a type 2 immune response, releasing cytokines from Th2 cells that account for features of asthma:

Answer 18

IL-4: IgE production (class switching of Bcells to IgE)
IL-5: activates eosinophils
IL-13: stimunates mucus production; activates B cells.

Question 19

Smoking alter the inflammation by:

Answer 19

It changing the type of cells. Usually largelly eosinophils but in someone that smokes, it become less eosinophilic and more neutrophilic.

Question 20

Cystic fibrosis is:

Answer 20

• A multi-system disease affeting the lungs, gastro-intersinal tract, pancreas, and others organs.
• An autosomal recessive disorder (need two copies of the gene, one from each parent)
• Caused by a genetic mutation in Cystic Fibrosis transmembrane regulator (CFTR) which cause sticky mucus to build up on the outside of the cell

Question 21

Cystic fibrosis transmembrane regulator (CFTR) role :

Answer 21

• Predominantly located on apical membrane of epithelia
• Regulates fluid and electrolyte transport - Chloride ions**
• Important for proper hydration of various organs
• Proper mucociliarly clearance

Question 22

There is more than 1000 disease-associated CFTR mutation, the most commun mutation is:

Answer 22

F508, a Class II defect (recognized the CFTR as misfolded and degraded after synthesis)

Question 23

Cystic Fibrosis pathophysiology:

Answer 23

1. The primary defect lead to defective ion transport
2. Leads to airway surface liquid depletion, and contribute to defective inflammation
3. Then will get mucus obstruction that will contribute to infection of the airways and inflammation.
4. Vicious Circle

Question 24

Cystic Fibrosis pathogenesis:

Answer 24

• Neutrophilic inflammation
• Prone to recurrent infection due to: Increase aGM1 (receptor for pseudomonas aeruginosa), decrease in CFTR, and decrease in antimicrobial properties.
• Increase infection + inflammation –> chronic infection –> tissue destruction (epithelial shedding+inflammation)

Question 25

Idiopathic Pulmonary Fibrosis (IPF) is:

Answer 25

• Rare, fatal, specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause.
• Lung become scarred, making it hard to take air into the lung.

Question 26

Histology of pulmonary fibrosis:

Answer 26

-The lung architecture completely changed, becoming completely fibrotic. (scar tissue)

Question 27

Pathogenesis of IPF in unknown, some theory:

Answer 27

• Injury (repetitive microinjury to the lung?)
• Abnormal repair response (Re-epithelialization to repair is abnormal)
• Mediators: TGf-B (cytokines playing a role in fibroblasts)
• Myofibroblasts (produce copious amounts of ECM)
• ECM (extracellular matrix) deposition (collagens,fibroblasts)

Question 28

Fibroblasts are the main effector cells, the 3 potential sources that can contribute to the disease are:

Answer 28

1. Resident interstitial lung fibroblast (activated by TGF-B and major source of myofibroblast)
2. Epithelial mesenchymal transition (Epithelial cell takes on features of a fibroblast to help drive the pathogenic process)
3. Fibrocytes from circulation (recruited to different organs, than enter and differentiate into myofibroblasts)

Question 29

Transforming growth factor (TGF)-B leading to pulmonary fibrosis:

Answer 29

• Become activated and bind to the receptor on the cell surface which activates a signaling cascade via phosphorylation.
• Resulting in activation of SMAD proteins
• This goes on the DNA sequences that transcriptionally regulates a number of ECM genes.
• Lead to ECM protein production.