Anatomy and Physiology
What is the conducting zone?
The conducting zone moves air. The respiratory zone begins with respiratory bronchioles and includes alveolar ducts, alveolar sacs, and alveoli, where gas exchange occurs.
What is innate immunity?
Adaptive immunity = slower initially, specific, diverse, and generates memory.
What is Type 2/T2 asthma?
Type 2 asthma is an inflammatory asthma phenotype driven mainly by Th2 cells and ILC2 cells, with production of IL-4, IL-5, and IL-13.
The β₂-adrenergic receptor causes...
Activation of this receptor causes:
Gs → adenylyl cyclase ↑ → cAMP ↑ → PKA ↑ → MLCK activity ↓ → airway smooth-muscle relaxation
These air-filled structures produce mucus that humidifies inhaled air and traps microorganisms, pollutants, dust, and debris, while cilia move the mucus toward the throat.
What are the sinuses?
What is a type II alveolar cell / ATII pneumocyte?
ATII cells produce pulmonary surfactant and can help replace damaged type I alveolar cells.
What are PRRs and what do they identify?
Pattern recognition receptors (PRRs) are host sensor proteins that detect microbial invaders and internal distress signals
• PRRs identify:
• Pathogen-Associated Molecular Patterns (PAMPs), including components of microbial cell walls such as lipopolysaccharides (LPS)
• Damage-Associated Molecular Patterns (DAMPs), including endogenous molecules released by stressed cells such as nuclear DNA, heat shock proteins,
and extracellular ATP
What are the early phase and late phase allergic responses?
Early phase
Occurs within minutes after allergen exposure.
The allergen cross-links IgE on mast cells, causing mast-cell degranulation and release of mediators such as:
These rapidly cause:
Late phase
Occurs several hours later and involves recruitment of inflammatory cells, especially eosinophils and Th2 cells.
These cells release cytokines and toxic mediators that cause:
What is the M3 muscarinic receptor?
- what does it cause and wha does it produce?
Activation of this receptor normally causes:
Gq → PLC → IP₃ → Ca²⁺ ↑ → calmodulin → MLCK activation → bronchoconstriction
Blocking this receptor therefore produces bronchodilation.
Remember...
β₂ agonist = promotes relaxation
M3 antagonist = blocks contraction
Activation of this adrenergic receptor produces vasoconstriction of nasal blood vessels, reducing mucosal swelling and nasal congestion.
What is the α₁-adrenergic receptor?
What is decreased intrapulmonary/alveolar pressure?
Diaphragm contracts → volume ↑ → pressure ↓ → air enters.
Describe nuetrophils, Balance in Neutrophil Activity, Dendritic cells, and the types of granulocytes
Neutrophils
• Most abundant white blood cell in the
body but short-lived
• Multi-nucleated with granules full of
enzymes/proteases
• First line of defense (first responders)
• Rush to site of injury/infection to
phagocytose pathogens and release
ROS, proteases, and neutrophil
extracellular traps (NETs) to catch and
kill pathogens
Balance in Neutrophil Activity
• Proper inflammatory response requires balance in neutrophil activity
• Too little neutrophil activity increase severity of infections and promote tumor growth
• Too much neutrophil activity can cause emphysema, airway remodeling, and excessive tissue injury
• Certain medications and nutritional deficiencies can reduce neutrophil numbers
• Smoking and bacterial infections can increase neutrophils
Dendritic Cells
• Located on the basolateral side of the epithelium
• Express pattern recognition receptors
• Project pseudopodia into the lumen of alveoli and
conducting airways to sample and engulf antigens
• Bridge innate and adaptive immunity by traveling
to lymph nodes and presenting antigen to T-cells
• During homeostasis, promote tolerance by
presenting self-antigens
Granulocytes
Mast Cells:
• Involved in allergic reactions
• Bind to allergen-specific IgE
• Release preformed mediators including histamine,
leukotrienes, cytokines upon allergen challenge
Eosinophils:
• Involved in allergic reactions
• Produce leukotrienes, eosinophil peroxidase, major
basic protein and promote inflammatory responses
What is airway remodeling?
Airway remodeling is the long-term structural change of the airway caused by repeated inflammation and injury in asthma.
Chronic inflammation can cause:
The result is persistent airway narrowing that may become less reversible over time.
One asthma medication inhibits 5-lipoxygenase, preventing leukotrienes from being produced. Another blocks the CysLT₁ receptor, preventing leukotrienes from producing their effects. Name one drug for each mechanism! What are these meds yall?
This molecule is the target of omalizumab, which prevents it from binding to high-affinity FcεRI receptors on mast cells and basophils
What is IgE?
What is alveolar collapse/atelectasis?
Surfactant ↓ surface tension, especially helping stabilize smaller alveoli and prevent collapse.
This interleukin is strongly associated with eosinophil growth, activation, and survival and is an important mediator in type 2 allergic inflammation
What is IL-5?
Describe chronic bronchitis and emphysema.
A. Chronic bronchitis →
Mucus hypersecretion + impaired cilia + narrowed airways → increased airway resistance
The primary problem is in the conducting airways.
B. Emphysema →
Destruction of alveolar walls and elastic fibers → ↓ surface area + ↓ elastic recoil → air trapping/hyperinflation
The primary problem is the alveoli and lung parenchyma.
______
Chronic bronchitis = AIRWAY problem
Emphysema = ALVEOLAR problem
This inhaler requires a patient to coordinate pressing the canister with slow inhalation. Adding a spacer or valved holding chamber can make administration easier and decrease medication deposition in the mouth and throat.
What is a pressurized metered-dose inhaler (pMDI)?
A patient smokes their first cigarette 15 minutes after waking and wants nicotine gum.
Identify:
What is decreased elastic recoil/elastance?
Emphysema destroys elastic tissue.
Normally:
Stretch lung → elastic recoil pulls it back inward → helps expiration.
With emphysema:
Elastic recoil ↓ → lungs don't spring back → air is harder to push out → air trapping/hyperinflation.
These two interleukins are especially important in allergic airway disease because one promotes IgE class switching, while the other contributes to mucus production and airway hyperresponsiveness.
What are IL-4 and IL-13?
Two patients have COPD. One has predominantly eosinophilic/type 2 inflammation, while the other has predominantly neutrophilic/Th1-Th17 inflammation. This patient would generally be expected to respond better to inhaled corticosteroids.
Who is the patient with eosinophilic/type 2 inflammation?
A patient has very weak inspiratory flow because of severe pulmonary disease. This type of inhaler would generally be a poorer choice because the patient must generate sufficient airflow to disperse and inhale the medication powder.
What is a dry-powder inhaler (DPI)?
This smoking-cessation medication is a partial agonist at α4β2 nicotinic acetylcholine receptors.
It provides enough receptor stimulation to reduce cravings and withdrawal, while preventing nicotine from producing its full rewarding effect if the patient smokes.
What is varenicline (Chantix)?
Mechanism:
Partial stimulation → withdrawal ↓
Blocks nicotine's full stimulation → smoking reward ↓