Basic Science applied to medicine

1. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
- Created with love
by Dr. Eashan Srivastava

2. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
AIRWAY INFLAMMATION
● Involves the cells that play prominent roles in the allergic response
● Allergen exposure via inhalation
● Production of specific IgE antibodies
- Created with love
by Dr. Eashan Srivastava

3. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
○ Overexpression of Th2 type T cell responses
● IgE antibodies bind to high-affinity receptors on mast cells
● When an allergen is subsequently inhaled
○ Cross links allergen-specific IgE antibodies on the mast cell surface
○ Degranulation and mediator release
● Early & Late phase reactions
○ Allergen inhalation by a sensitized individual
○ Within minutes
■ Bronchoconstriction
■ Release of mast cell mediators including histamine, prostaglandin D2,
and leukotrienes (LTC4, D4, and E4)
○ Hours later
■ Bronchoconstriction
■ Recruitment of inflammatory
● Eosinophil
● Basophil
● Neutrophil,
● T-cells
● EOSINOPHILS
● Most characteristic cell in asthma
● Produces several mediators
○ Major basic protein
○ Eosinophil-derived neurotoxin
○ Eosinophil peroxidase
○ Eosinophil cationic protein
○ Can damage airway epithelium
● Recruited or activated by IL 5
● Mast cells
○ Producing bronchoconstricting mediators
■ Histamine
■ Prostaglandins
■ Leukotrienes
■ TNF-alpha= Recruitment and activation of inflammatory cells
- Created with love
by Dr. Eashan Srivastava

4. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
● Th2 lymphocytes
○ Produce IL-3, IL-4, IL-5, IL-13, and GM-CSF
○ IL-3
■ Survival factor for eosinophils and basophils
○ IL-4
■ Differentiation of uncommitted T cells into Th2 cells
■ IgE class switch
■ VCAM-1 expression that mediates eosinophil, basophil recruitment
○ IL-5
■ Increased eosinophil production and survival
○ IL-13
■ Mucous gland hyperplasia
■ Airway fibrosis
■ Remodeling
EPITHELIAL-MESENCHYMAL CONTRIBUTION
● "epithelial-mesenchymal trophic unit" plays a central role in inflammation and remodeling
● According to this theory, structural cells, particularly bronchial epithelial cells, fibroblasts,
smooth muscle, and vascular endothelial cells, elaborate mediators and cytokines that
contribute to inflammation and/or airway remodeling
PHYSIOLOGY OF AIRFLOW OBSTRUCTION
● Smooth muscle
○ Contraction of airway smooth muscle accounts for airflow limitation
○ Mediated by
■ Reflex neural mechanisms
■ Mediators
● Leukotrienes C4, D4, and E4
● Histamine
● Prostaglandins
○ Bronchial thermoplasty
- Created with love
by Dr. Eashan Srivastava

5. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
■ Technique that applies radiofrequency waves to the airways during
bronchoscopy to decrease large airway smooth muscle mass
■ Support a central role for ASM in large airways in the pathogenesis
● Bronchial hyperresponsiveness
○ Reversible airflow obstruction
○ Exaggerated constrictor response to allergens
○ Calculated by the dose response to pharmacologic agents
■ Dose of Methacholine or histamine causing a 20% fall in FEV​1
○ Mechanism
■ Altered smooth muscle function or mass
■ Inflammatory mediators
■ Loss of airway-parenchymal interdependence
■ Loss of a bronchodilating effect of deep breaths
■ Enhanced sensitivity of neural pathways
AIRWAY REMODELING
● Patients may have irreversible airflow obstruction
● Airway remodeling refers to structural changes in the airways that may cause irreversible
airflow limitation, superimposed on the effects of inflammation and smooth muscle
contraction described above
● Histopathology
○ Loss of the normal pseudostratified structure of airway epithelium
○ Increase in the proportion of mucous-producing goblet cells
○ Fibrosis
○ Increased numbers of myofibroblasts
○ Increased airway smooth muscle mass
○ Increased extracellular matrix
MODULATORY FACTORS
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by Dr. Eashan Srivastava

6. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
Genetic factors
Environmental factors
● Air pollution
● Allergens (eg, dust mite, occupational allergens)
● Cigarette smoke
● Endotoxin
Infectious agents
Both bacterial and viral respiratory tract infections have been associated with increased risk of
asthma
- Created with love
by Dr. Eashan Srivastava