L3 Lung structure and airway disease Flashcards
The respiratory system includes: (list)
- Lungs
- Airways
- Blood vessels
- Gas exchange
3 main divisions of the respiratory tract
- Conducting airways
- Resistance airways
- Respiratory Airways
Whats part of the conducting airway
- Trachea
- Primary bronchus
- Secondary bronchus
Whats part of the resistance airway?
- Bronchiole (<=1mm)
- Terminal Bronchiole
Whats part of the Respiratory airway?
- Alveolar duct
- Alveolar sac
- Respiratory Bronchiole
(cartilage) Bronchus divides to
Bronchiole (no catilage)
Bronchus and Bronchiole contain
- Glands (mucus)
- Smooth muscle epithelium
- Cartilage
- Connective tissue and elastic fibre
Alveolar airways contain
- Respiratory bronchiole
- Smooth muscle
- alveolar duct
- Alveolar sac
- Arteriole
- Alveoli
- Interalveolar septum
Route of blood in the alveolar cappillary
O2 in lumen
↓
Surfactant
↓
Aairway epithelium fused basil lamina vascular epithelium
↓
Capillary
↓
Binds to haemoglobin
Distance O2 travels in capillary
0.2-0.6µm
Pulmonary arteries carry blood where?
To the lungs
Pulmonary veins carry blood where?
From the lungs
Pulmonary veins carries what?
Oxygen (O2)
Pulmonary arteries carry what?
Carbon Dioxide (CO2)
Bronchial arteries do what to blood and where
- supply
- trachea, bronchi, bronchial branches, esophagus, and visceral pleura
Bronchial veins do what to blood and where
- Drain from airways
Bronchial veins carry what in blood
Carbon Dioxide (CO2)
Bronchial arteries carry what in blood?
Oxygen (O2)
Airway epithelium type
Pseudostratified columnar
What does airway epithelium do?
- Physical barrier
- Housekeeping
- Catabolic and anabolic metabolism
Airway epithelium
Physical barrier
- inhibits penetration of inhaled noxious substances
- allergens, mast cell-derived mediators, particulate
matter, irritant molecules
– prevents access to submucosa - nerves, vascular tissue, airway smooth muscle
Airway epithelium
Housekeeping role
– cilia beat synchronously, propel mucus towards throat
– mucus and particulate matter continually cleared
– ciliated cells damaged first in asthma
Airway epithelium
Catabolic metabolism
- Active
- via cytochrome P450 system
- peptide degradation via neutral endopeptidase
- > neuropeptised are degraded and are proteins with airway activity.
- – protects sensitive targets - nerves, muscle, glands
Airway epithelium
Anabolic metabolism
– synthesis of inhibitory mediators – PGE2 (relaxes airway muscle)
– rich source of peptides – endothelin (growth factor)
– produces pro-inflammatory cytokines
Airway nerves
excitatory and inhibitory
Contraction and relaxation
Airway nerves
Cholinergic
- Excitatory
- Releases ACh
- Dom neiral pathway
- Role in regulating airway smooth muscle tone and mucus production
Airway nerves
Noradrenergic
- Inhibitory
- Relaxation
- Noradrenaline decreases smooth muscle tone
- no major role in main bronchi
Airway nerves
Inhibitory nonadrenergic noncholinergic (iNANC)
– release nitric oxide (NO)
– innervates smooth muscle directly
– relaxation
Airway Nerves
Excitatory nonadrenergic noncholinergic (eNANC)
– release neuropeptides e.g., substance P, neurokinin A – increase airway tone, secretion of mucus and microvascular
leakage
– capsaicin in pepper spray
What is asthma?
Chronic inflammatory disease of the airways
characterised by bronchial obstruction and airflow limitation.
What characteristic in asthma are reversible
Bronchial obstruction and airflow limitation.
Either spontaneously or with treatment
Asthma characteristics/symp
– shortness of breath, wheeze, tight chest, cough
– allergic, occupational, exercise-induced, aspirin
– mild, moderate, severe
Allegeric response in asthma [Early phase]
- Decrease in Forced expiratory vol in 1 second (FEV1), peak at 30-40 min, resolves in 2-3 hrs
- mast cell-derived histamine and leukotrienes (by the decrease if FEV1)
- Contract
Allegeric response in asthma [Late phase]
- release of inflammatory mediators cause submucosal oedema, airway wall swelling, secretion of mucus
- epithelium remodelling, airway muscle
hypertrophy/hyperplasia, subepithelial fibrosis
Submucosal oedema
Leaking of plasma from microvessels of bronchiole circulation that allows airway to swell.
Bronchial Obstruction in Asthma
– ↑ airway smooth muscle tone
– ↑ secretion of mucus
– shedding of the epithelium and accumulation of debris in airway lumen
– oedema and swelling of the submucosa
– airway smooth muscle hypertrophy (↑ cell size) and hyperplasia ↑ cell number)
– sub-epithelial fibrosis
What are asthmaics hyperrespovsice to
– methacholine, histamine, cold air
– allergic late phase response, respiratory viruses
Airway resistance
– resistance to airflow is inversely proportional to the radius of the lumen raised to the fourth power
* R 1/inverse r4
Airway narrowing
– ↑ airway smooth muscle force and/or mass
– microvascular leakage from post-capillary venules and resultant oedema
Histamine and asthma
- Stored in mast cells and basophils
– released in response to appropriate allergen
– early phase response - Bronchoconstriction, airway wall oedema
– bronchial obstruction and airflow limitation
- Histamine (H1) receptor antagonists (antihistamines) asthma
– seasonal allergies e.g., hay fever
– not useful in asthma
- Histamine (H4) receptor antagonists in development in asthma
– asthma, atopic dermatitis, psoriasis
Leukotrienes asthma mediator
- Family of lipid mediators derived from arachidonic acid metabolism
- Released in response to allergen exposure
– early and late phase response - LTB4 family is a chemoattractant for inflammatory cells
- LTd,e,c4
- Bronchoconstrictors, mucus secretion↑, incude mediator from inflammatory cells
Chronic Obstructive Pulmonary Disease (COPD)
- Progressive degenerative disease causes death
– debilitating symptoms, shortens lifespan
– primary causes – tobacco smoking and air pollution - most important therapy is smoking cessation
- indoor air pollution – heating + cooking
- outdoor air pollution
- occupational dusts, chemicals, vapours, irritants,
fumes
- COPD =
chronic bronchitis + emphysema
Combination Bronchodilator –
Treatment of COPD
Ipratropium bromide (muscarinic antagonist)
+ salbutamol (b2-adrenoceptor agonist)
Triple Combination Therapy –
Treatment of COPD
Glucocorticoid +
Muscarinic Receptor Antagonist
+ Long Acting b2-Agonist
Chronic Bronchitis Features
- Inflammatory disease with irreversible airflow limitation
- Hypersecretion of bronchial mucus
– hypertrophy & hyperplasia of bronchial mucus-secreting cells
– chronic cough, excessive sputum - Secondary respiratory infections
– excessive mucus production
Chronic Bronchitis Treatment
* Selective phosphodiesterase IV inhibitor (roflumilast)
– improves lung function
– ↓ frequency of exacerbations
– targets underlying inflammation
Chronic Bronchitis Treatment
Drugs provide symptom relief
- b2-adrenoceptor agonists
– muscarinic antagonists
– glucocorticoids
– mucokinetic drugs ( mucus viscosity)
– antibiotics (secondary infections)
Emphysema
- Degenerative, peripheral lung disease
- Involves destruction of alveolar membranes
– causes severe impairment of: - oxygen delivery
- carbon dioxide clearance
- Often associated with smoking and chronic bronchitis
