Pathophysiology of respiratory diseases pt 1 Flashcards
What is asthma
asthma is a chronic, inflammatory and obstructive disease of the airways
Explain what airway inflammation does
airway inflammation increases airway resistance and decreases airflow
Explain what occurs on in asthmatic airway
-contraction of smooth muscle
-excess mucus secretion
-oedema/swelling
-irritation of sensory neurons
What is the overall effect of this
overall effect is decreased luminal area
Increased air resistance leads to decreased airflow
What does contraction of airway smooth muscle cells lead to
-contraction of airway smooth muscle cells lead to airway obstruction and increased airway resistance
-during contraction: there is a contracted and smaller SM cell and decreased luminal area and flow and increased resistance
-during relaxation: increased lumen diameter, relaxed and larger SM cell
-increased luminal urea and flow and decreased resistance
What do bronchodilators do
-bronchodilators reverse airway obstruction by causing ASMCs to relax
How does inflammation cause airway smooth muscle cells (ASMC) to contract
1) Inflammatory mediators (like cysLTs, ACh, and PGs — shown as little red and yellow circles) bind to a special G protein-coupled receptor on the cell surface (like M3 receptors).
This activates a signaling protein inside the cell called Gq.
Gq triggers intracellular signaling pathways that lead to the release of calcium (Ca²⁺) from storage inside the cell (specifically from the sarcoplasmic reticulum — like a calcium warehouse in the cell).
The increase in Ca²⁺ mobilization and sensitivity inside the cell makes the muscle contract.
➡️ This leads to muscle contraction — in this case, narrowing the airways (like in asthma).
How does a B2 agonist help these muscles relax
Inflammatory mediators (like cysLTs, ACh, and PGs — shown as little red and yellow circles) bind to a special G protein-coupled receptor on the cell surface (like M3 receptors).
This activates a signaling protein inside the cell called Gq.
Gq triggers intracellular signaling pathways that lead to the release of calcium (Ca²⁺) from storage inside the cell (specifically from the sarcoplasmic reticulum — like a calcium warehouse in the cell).
The increase in Ca²⁺ mobilization and sensitivity inside the cell makes the muscle contract.
➡️ This leads to muscle contraction — in this case, narrowing the airways (like in asthma).
Explain allergen sensitisation occurs
-allergen exposure
-allergen encountered and processed by adaptive immune system
-IgE antibodies generated immune system ‘primed’
Explain the allergic response
-subsequent as allergen exposure
-allergen binds antibodies —-> immune cell activation ——> inflammatory response
What happens if someone with asthma breathes in something their allergic to?
1) The “bad guy” arrives: The inhaled allergen enters the tissue of their airways.
A security alarm goes off: These allergens bump into special cells called mast cells that have “traps” (called IgE) on their surface, specifically waiting for this allergen. When the allergen binds to the IgE, it’s like setting off an alarm.
The alarm triggers a release: The mast cell then bursts open (degranulation) and releases tiny “messengers” called inflammatory mediators (like PGs, LTs, and chemokines). Think of these as little shouting signals that cause trouble.
More trouble arrives: These messengers attract other cells called eosinophils to the airways.
Eosinophils also cause problems: These eosinophils also release their own set of harmful substances (inflammatory mediators like ROS, enzymes, and leukotrienes) which add to the inflammation.
The airways get narrow and clogged: All this inflammation causes the smooth muscles around the airways to contract, making them squeeze tight. There’s also excess mucus secretion and swelling (oedema), further blocking the airways.
Breathing becomes difficult: As a result, the lumen diameter (the open space inside the airway) gets smaller, making it harder for air to flow in and out. This increases resistance and decreases airflow, leading to asthma symptoms like wheezing and shortness of breath.
How do corticosteroid drugs reduce asthma inflammation
Corticosteroid drugs reduce asthma inflammation by modulating the function of multiple mine and structural cells
Explain how corticosteroid drugs affect different types of inflammatory cells
-reduces numbers of eosinophils
-reduces number of cytokines in T lymphocyte
-reduces numbers of mast cells
-reduces number of cytokines in macrophage
-reduces number of dendritic cells
Explain how corticosteroid drugs affect different types of structural cells
-reduces number of cytokines mediators in epithelial cell
-reduces leak in endothelial cells
-increases B2 receptors in airway smooth muscle
-decreased mucus secretion in mucus gland
How do corticosteroids work inside the cell to reduce inflammation
The Drug Enters: The corticosteroid drug easily passes through the cell’s outer layer and finds its target inside, which is a glucocorticoid receptor.
They Join Up: The corticosteroid (key) binds to the glucocorticoid receptor (lock). Once they’re connected, they form a drug-receptor complex.
Moving to the Command Center: This complex then moves into the cell’s command center, called the nucleus, where all the genetic information (DNA) is stored.
Changing Instructions: Inside the nucleus, the drug-receptor complex binds to specific parts of the DNA called regulatory sites. This binding tells the DNA to change how it makes certain proteins.
Making New Proteins (or Less of Others): The DNA then creates mRNA, which is like a messenger carrying the new instructions. This mRNA goes out of the nucleus, and the cell uses these instructions to build new proteins.
Controlling Inflammation: These new proteins (or the lack of other proteins) are what actually reduce inflammation. For example, corticosteroids can increase the production of proteins that fight inflammation (anti-inflammatory genes) and decrease the production of proteins that cause inflammation (pro-inflammatory genes).
