Pathophysiology of Asthma, COPD, and Cystic Fibrosis

Question 1

Which process is required for the mast cell degranulation often seen in the early reaction of asthma?

Answer 1

cross linking of Fc receptors for IgE

Question 2

What two events (other than mast cell degranulation) occur in the early reaction of asthma? (hint: think of inflammatory processes)

Answer 2

bronchial smooth muscle constriction and vascular leakage

Question 3

What are the events of the late reaction of asthma?

Answer 3

(1) sustained bronchoconstriction
(2) eosinophil infiltration
(3) mucus hypersecretion
(4) TH2 cell activation

Question 4

Exposure to asthma-inducing antigens activates _______ and _______.

Answer 4

mast cells, T lymphocytes

Question 5

The major players in the development of an asthma-type reaction that are released by T lymphocytes are _________.

Answer 5

cytokines

Question 6

What are the main receptors involved in the development of goblet cell hyperplasia? maintenance of hyperplasia?

Answer 6

development: EGFR and CACL
maintenance: Bcl-2

Question 7

The ______ polymorphism in the _______ receptor mediates enhanced response to _______.

Answer 7

R576, IL-4alpha, IL-13

Question 8

What is the effect of IL-13 most relevant to asthma?

Answer 8

mucus hypersecretion

Question 9

What is the role of periostin in asthma pathophysiology?

Answer 9

Periostin is an extracellular matrix protein induced by IL-13 and IL-4. These interleukins activate fibroblasts to secrete periostin, which acts as a ligand for intern molecules that facilitate immune cell adhesion and migration in bronchial tissue.

Question 10

Describe the three elements of airway remodeling in asthma.

Answer 10

(1) epithelium: mucus cell hypersecretion and hyperplasia
(2) smooth muscle hypertrophy
(3) basement membrane thickening due to fibroblast activation

Question 11

Contrast COPD with asthma in regards to time of onset, triggers, and persistence of symptoms.

Answer 11

COPD: onset later in life (usually after 40), no specific triggers, chronic symptoms, progressive in nature

asthma: occurs earlier in life, specific triggers, episodic

Question 12

Describe the changes in airways that occur in COPD and what cells are responsible.

Answer 12

small airway fibrosis (fibroblast mediated), alveolar destruction and enlargement (macrophage, TH1, and neutrophil mediated), mucus hypersecretion (goblet cell mediated)

Question 13

A genetic deficiency in _____________ can manifest as COPD.

Answer 13

alpha-1-antitrypsin

Question 14

Cystic fibrosis involves a mutation in the ______ gene.

Answer 14

CFTR

Question 15

Patients with a CFTR mutation produce mucus that is _________

Answer 15

abnormally thick and viscous

Question 16

What is the consequence of abnormally thick mucus found in CF?

Answer 16

(1) more easily harbors pathogens
(2) obstructs airways
(3) obstructs pancreatic duct, interfering with digestion

Question 17

In which 3 locations is CFTR normally expressed?

Answer 17

(1) pancreatic duct epithelium
(2) sweat duct epithelium
(3) airway epithelium

Question 18

What is CFTR’s normal function (in airway and sweat duct epithelium)?

Answer 18

airways: inhibits Na influx mediated by ENaC channel and facilitates Cl export from cells into mucus

sweat duct: follows Na influx from sweat to maintain charge balance

Question 19

In both airways and in sweat duct epithelium, explain how loss of CFTR function affects the local area.

Answer 19

In the airways, faulty CFTR cannot prohibit Na influx AND cannot export Cl into mucus. Both of these reduce the ion concentration of mucus, and, thus, reduce the water concentration, thickening the mucus.

In sweat duct epithelium, chloride normally follows sodium influx through ENaC. When CFTR is inhibited here, sodium cannot be pulled from sweat, so NaCl concentration is increased.