Week 16 RAT

OMK Block 3

Airflow Principle

Air moves from regions of higher pressure to lower pressure; the pressure gradient drives ventilation.

Driving Pressure in Breathing

The difference between atmospheric pressure and alveolar pressure determines the direction of airflow.

Intrapleural Pressure

The pressure inside the pleural cavity; normally negative (~ -4 mmHg) to prevent lung collapse.

Transmural Pressure

The difference between alveolar pressure and intrapleural pressure; represents the distending pressure keeping alveoli open.

Pneumothorax Mechanism

When intrapleural pressure equals or exceeds atmospheric pressure, lung collapse occurs due to loss of negative pressure.

Alveolar Pressure During Inspiration

Thoracic expansion makes alveolar pressure slightly negative, allowing air to flow into the lungs.

Alveolar Pressure During Expiration

Thoracic volume decreases, alveolar pressure rises slightly above atmospheric, forcing air out.

Quiet Inspiration

The diaphragm contracts and external intercostals elevate ribs, expanding thoracic volume.

Forced Inspiration

Accessory muscles (sternocleidomastoid, scalenes, pectoralis minor, serratus anterior) assist when breathing effort increases.

Quiet Expiration

Occurs passively through relaxation of inspiratory muscles and elastic recoil of the lungs.

Active Expiration

Uses internal intercostals and abdominal muscles to compress the thorax and expel air forcefully.

Compliance

Measure of lung stretchability; reduced in fibrosis, increased in emphysema.

Airway Resistance

Determined mainly by airway radius; small decreases in radius cause large drops in airflow (Poiseuille’s law).

Dynamic Airway Compression

During forced expiration, high intrapleural pressure narrows airways, limiting flow even with effort.

Laminar vs Turbulent Flow

Laminar flow is smooth and efficient; turbulent flow increases resistance and energy cost of breathing.

Work of Breathing

The energy needed to overcome airway resistance and elastic recoil during respiration.

Types of Respiratory Pathogens

Pathogens include viruses (most common), bacteria, fungi, and rarely parasites.

Common Viral URIs

Rhinovirus, coronavirus, adenovirus, parainfluenza, and influenza commonly infect the upper respiratory tract.

Common Bacterial URIs

Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent bacterial causes.

Pharyngitis Definition

Inflammation of the pharynx (sore throat) caused by viral or bacterial infection.

Strep Throat Definition

Specific type of bacterial pharyngitis caused by Group A Streptococcus (Strep pyogenes).

Viral vs Bacterial Pharyngitis

Viral: gradual onset, cough, congestion; Bacterial: sudden onset, fever, exudates, tender cervical nodes, no cough.

URI Risk Factors

Include young or elderly age, smoking, crowded environments, immune suppression, allergies, and poor hygiene.

Lincosamide Mechanism

Clindamycin binds the 50S ribosomal subunit, inhibiting protein synthesis in Gram+ and anaerobic bacteria.

Clindamycin Adverse Effect

May cause C. difficile–associated pseudomembranous colitis due to alteration of gut flora.

Macrolide Mechanism

Macrolides (erythromycin, azithromycin, clarithromycin) bind the 50S subunit to inhibit bacterial translocation.

Macrolide Coverage

Covers Gram+, some Gram−, and atypical organisms such as Mycoplasma, Chlamydia, and Legionella.

Macrolide Adverse Effects

Can cause QT prolongation, GI upset, and CYP3A4 drug interactions (especially erythromycin).

Tetracycline Mechanism

Tetracyclines (doxycycline, minocycline) bind the 30S subunit, preventing tRNA attachment and protein synthesis.

Tetracycline Coverage

Broad-spectrum; active against Gram+, Gram−, and atypical organisms (Rickettsia, Chlamydia, Mycoplasma).

Tetracycline Adverse Effects

Cause tooth discoloration, photosensitivity, and GI irritation; avoid in pregnancy and children under 8 years.

Atopy Definition

Genetic tendency to produce IgE antibodies in response to normally harmless environmental allergens.

IgE Formation Process

Allergen exposure → antigen-presenting cell activation → Th2 cell differentiation → IL-4 and IL-13 promote B-cell class switching to IgE.

Sensitization Phase of Asthma

Initial allergen exposure induces IgE production and binding to mast cells, priming them for re-exposure.

Elicitation Phase of Asthma

Re-exposure causes allergen binding to IgE on mast cells → crosslinking → degranulation → inflammation and bronchoconstriction.

Mast Cell Degranulation Mechanism

Crosslinked IgE on mast cells triggers calcium influx and release of histamine, leukotrienes, and prostaglandins.

Mast Cell Mediators

Histamine (rapid bronchoconstriction, mucus), leukotrienes (prolonged constriction), prostaglandins (vasodilation), cytokines (inflammation).

IL-4, IL-5, IL-13 Roles in Asthma

IL-4 promotes IgE production, IL-5 recruits eosinophils, IL-13 increases mucus and contributes to airway remodeling.

β2-Adrenergic Receptor Function

Stimulation increases cAMP in smooth muscle → bronchodilation and improved airflow.

Muscarinic (M3) Receptor Function

Activation increases intracellular calcium → bronchoconstriction and mucus secretion.

β2 Receptor Pathway

β2 receptor activates Gs → increases adenylyl cyclase activity → raises cAMP → activates PKA → smooth muscle relaxation.

M3 Receptor Pathway

M3 receptor activates Gq → increases IP3 and DAG → raises Ca2+ → smooth muscle contraction.

Adrenergic vs Cholinergic Airway Control

Adrenergic (β2) stimulation relaxes airways; cholinergic (M3) stimulation constricts them.

Albuterol Mechanism

Short-acting β2 agonist that relaxes bronchial smooth muscle by increasing cAMP; provides rapid bronchodilation.

Albuterol Advantages

β2-selective → minimal cardiac effects; longer duration and safer than epinephrine, ephedrine, or isoproterenol.

Epinephrine in Asthma

Nonselective α/β agonist; provides bronchodilation but causes tachycardia and hypertension—used mainly for anaphylaxis.

Isoproterenol Limitation

Nonselective β agonist; causes unwanted β1 cardiac stimulation despite bronchodilation.

Atopic Asthma Overview

Chronic inflammatory airway disease driven by IgE-mediated hypersensitivity and Th2 cytokine signaling.