RESP- Pathophysiology of Respiratory Diseases I

Question 1

how do allergic responses develop

Answer 1

allergen exposure
allergen encountered and processed by adaptive immune system
antibodies generated; immune system primed
subsequent allergen exposure
allergen binds to antibodies leading to immune cell activation and an inflammatory response
this produces symptoms

Question 2

how is an asthmatic response triggered

Answer 2

inhaled allergen enters airway tissues
allergen binds to IgE on mast cells inducing degranulation
attracts eosinophils (inflammatory mediators, ROS, Enzymes etc.) which degranulate
this degranulation causes contraction of smooth muscle cells, excess mucus secretion, oedema and swelling

leading to a decrease in airflow

Question 3

in an asthmatic response, what attracts eosinophils to the airways

Answer 3

T helper 2 cell activation - IL-4, IL-5, IL-13

IL-5 acts as a chemoattractant which recruits eosinophil to the airways which degranulate
airway inflammation reduces airflow and generates symptoms

Question 4

what are the key pathophysiological changes associated with asthma

Answer 4

inflammation - allergen inhalation, excercise, immune system response, airway inflammation

airway dysfunction - impaired airway function, symptoms- wheeze, cough, dyspnoea, decrease FEV1/FVC

Question 5

what produces asthmatic airway symptoms

Answer 5

contraction of smooth muscle
excess mucus secretion
oedema / swelling
irritation of sensory neurons (cough)

overall effect = decrease luminal area = increased airway resistance = decreased airflow = symptoms

Question 6

how do inflammatory mediators induce ASMC contraction

Answer 6

contractile mediators (cysLTs, Ach, PGs) act on G protein-coupled receptors (M3)

invoke intracellular signalling pathways - stimulation of sarcoplasmic reticulum - increase calcium mobilisation and sensitivity - creates muscle contraction

Question 7

what is the mechanism of action for salbutamol

Answer 7

salbutamol = beta 2 agonist
bind to B2 receptor (Gs)
activated adenylyl cyclase which causes the conversion of ATP to cAMP which activates PKA which decreases calcium mobilisation and sensitivity

this produces muscle relaxation

Question 8

what inflammatory cells are involved in asthmatic inflammation

Answer 8

Eosinophils- apoptosis
T lymphocytes 
mast cells
macrophages
dendritic cells

Question 9

what structural cells are involved in asthmatic inflammation

Answer 9

epithelial cells - cytokine mediators
endothelial cells - decrease leak
airway smooth muscle
mucus glands

Question 10

what is the mechanism of action for corticosteroids

Answer 10

diffuse through membrane and binds to intracellular GR

this then translocases to the nucleus

drug receptor complex binds to DNA and affects transcription

altered transcription of a gene = altered translation into a protein

corticosteroids increase or decrease expression depending on the specific gene/protein

Question 11

what are the types of asthma

Answer 11

aspirin associated respiratory disease
allergic bronchopulmonary mycosis
cold air/ excercise induced asthma
allergic asthma