Asthma & COPD Flashcards
Respiration Functions of Lungs:
- Make O2 available for metabolism (“internal respiration”)
- ventilation (6000L/day at rest)
- gas exchange (lung)
- transport to tissues - Remove CO2 - metabolic byproduct
- transport from tissues to lung
- gas exchange
- expiration
Non-respiratory functions of lungs:
defence against infection, particulate matter & noxious chemicals
- lung ventilation ~6000L per day without exertion
- pulmonary capillary bed is only 1 in body through which entire blood supply flows! (therefore lung is a high risk area (non-sterile)
Why is the lungs deemed a high risk area?
pulmonary capillary bed is only 1 in body through which entire blood supply flows! (therefore lung is a high risk area (non-sterile)
What are non-specific defenses?
clearance - cough, mucociliary escalator (mucous, bugs, debri, etc. gets pushed up & coughed out)
secretions - mucous, surfactant
cellular - epithelium, phagocytes
biochemical - proteinase inhibitors (a1-antitrypsin), antioxidants
What is a1-antitypsin?
its genotype determines whether someone who smokes will get COPD for ex
What are specific immune defenses?
antibody mediated immunity
- b cells
antigen presentation
- dendritic, epithelial cells & macrophages
cell mediated immunity
- regulate local inflammation
- t-lymphocytes, mast cells, eosinophils
What is the path of airflow?
mouth/nose –> larynx –> trachea –> airways –> alveolae
What are features of the bronchi?
- cartilage in wall
- airway smooth muscle encircle
- Ciliated psuedostratified epithelium
- Mucous glands
What are features of Bronchioles?
No cartilage with reducing smooth muscle, cilia & mucous glands
Respiratory bronchioles:
• No smooth muscle or cilia
• First alveolar buds
What are features of Alveolar Sacs?
• Type I and II epithelium
• Surfactant (surface tension reducing agent)
• Gas exchange!
What do the vagus (parasympathetic) fibers do?
(cholinergic)
ACh regulation:
- Muscarinic 2 receptors (M2R)
- Muscarinic 3 receptors (M3R)
- stimulate mucous secretion from glands
- stimulates contraction of airways smooth muscle
- stimulates vasodilation
What do the sympathetic fibres do?
(adrenergic)
norepinephrine regulation:
- B2 adrenergic receptors
- A1 adrenergic receptors
- causes inhibition of mucous glands
- causes dilation of airways smooth muscle
- causes vasoconstriction
What pathway do anticholinertics inhibit for Asthma/COPD?
the parasymp. ganglion releasing ACh which binds to M3-receptors to trigger rxn - it prevents constriction
Where is the greatest resistance in the lungs & how does it relate to total cross-sectional area?
• Greatest resistance: 2nd-5th generation airways (conducting)
• Airflow resistance inversely ~ to total cross-sectional area
- meaning: if a few small airways collapse; won’t have as huge of an effect as a couple of large ones
Features of Asthma:
- Thickened airway smooth muscle & mucus plugging
- Airway hyperresponsiveness (bronchoconstriction)
- Airway wall swelling –> edema
Features of Chronic Obstructive Pulmonary Disease (COPD):
Chronic bronchitis:
- Smoking related chronic inflammation of lower airways
- Airway edema & mucus plugging
- Airway hyperresponsiveness (bronchoconstriction)
(similar to asthma but trigger is diff.)
Features of Chronic Obstructive Pulmonary Disease (COPD):
Emphysema:
- Loss and collapse of terminal bronchioles (tiny airways)
- Alveolar wall destruction(trypsin mediated)
– b/c of overwhelmed antitrypsin mech’s
What are airway resistance determinants?
radius and patency (ability to stay open rather than collapse) of conducting airways – Contraction of airway smooth muscle
– Mucous plugging
– Airway wall remodeling (physical change over time)
Smaller radius, ___ R
higher
Higher R, ___ air flow
less
Bronchoconstriction
Pathologic, physical, physiologic, & pharmacologic dynamic control
Pathologic
- Allergen, histamine
Physical
- Mucous, edema
- Airway collapse
Physiologic
- Parasympathetic stimulation
- Local decrease CO2
Pharmacologic
- Methacholine (binds to M3 receptors); triggers constriction
Bronchodilation
Pathologic, physical, physiologic, & pharmacologic dynamic control
Pathologic
- None
Physical
- None
Physiologic
- Sympathetic
neural stim
- Hormone (adrenaline)
- Local increase CO2 (cause opening)
Pharmacologic
- β2 adrenergic receptor ligands (salbutamol, salmeterol) (relax smooth muscle cells)
What is lost with emphysema (COPD)?
radial traction - b/c lung is being broken down
Larger lung has lower R; air flows greater
Compliance:
a measure of the dispensability of a structure - the degree that volume changes in response to a change in pressure = ∆V/∆P
Compliance is a determinant of airway-lung interpendence:
• Deep breath stretches open airways
• Lung stiffness keep airways open when
exhaling
Lung elastic recoil determined by:
• Elastic fibres in lung interstitium (collagen &
elastin)
• Surface tension of alveolar lining fluid
(surfactant)
Emphysema:
increased lung compliance due to tissue destruction
• reduced interdependence (airway-lung tethering)
• airways collapse more easily during exhale
• breathe at high lung volume (hyperinflation)
steeper the sloop - v. compliant (therefore elastic/stiff)
Spirometry
performed using a spirometer to measures volume of air moved during inspiration and expiration maneuvers (mL air/min=flow)
(measures airflow)
Functional residual capacity (FRC):
gas in the lungs at the end of a resting tidal breath
(volume you go down to when you exhale - v. small for someone with condition)
(Forced) Vital capacity (VC or FVC):
total amount of gas that can be exhaled after a maximal inhalation
(take deepest breath & then exhale all you can - it determines if airflow resis. has changed)
What is the Forced Vital Capacity Maneuver?
Standard test to assess presence of lung disease: (distinguish’s b/t)
• Obstructive (asthma; emphysema; chronic bronchitis)
• Restrictive (idiopathic pulmonary fibrosis, ILD)
FVC maneuver:
• forced inhalation from FRC to TLC (~1 second) - breath in as much as you can
• follow by forceful exhalation from TLC to RV (~5 seconds) (blow it all out - last 3-4 secs are difficult)
Using the FVC Maneuver one can determine:
FVC - forced vital capacity. Maximum amount of air forcibly expired after maximum inspiration (how much air can move in & out of lung in total)
FEV1 – volume of gas exhaled during first second (forced expiratory volume in 1 second) (healthy ~ 80% of FVC)
FVC Maneuver: Airway Obstruction
In Asthma or COPD:
•FEV1:FVC < 70% (if below than asthma or COPD is likely)
• FEV1 decreased
- airway resistance increased
• FVC reduced in severe disease (due to
hyperinflation in COPD) so need FEV1:FVC to isolate airway function!
Air has to get to ____ & its not when its severe
alveoli
What is Obstructive Airway Disease - Asthma?
1 reason children go to ER each year
A disorder of the airways characterized by paroxysmal or persistent symptoms (dyspnea, chest tightness, wheeze and cough) with variable airflow limitation & airway hyperresponsiveness to allergic and non-allergic stimuli
• Chronic airway eosinophil/neutrophil inflammation with REVERSIBLE airflow limitation (airway constriction, edema, mucous)
• Without appropriate treatment can be progressive – develop airway remodeling linked with FIXED airway obstruction
Asthma shifts to right on curve, so higher R, due to what?
• Allergy and inflammation
• Mucus production
• Structural remodeling
• Smooth muscle contraction
Asthma shifts to right on curve, so higher R, due to what?
• Allergy and inflammation
• Mucus production
• Structural remodeling
• Smooth muscle contraction
Risk factors for Asthma
Predisposition:
• atopy
• gender
• genetics
Causal Factors:
• in/outdoor allergens
• occupational sensitizers
• respiratory infection
Contributing Factors:
• respiratory infection
• air pollution
• smoking
Triggers:
• smoke & chemical fumes
• cold air, exercise
• aero- & food allergens
What does a Typical allergen response look like?
• Antigen presentation (innate immunity)
• Tcell maturation & activation (Th1, 2, 17)
• Cytokine and chemokine release
• B cells mature: antibodies (adaptive)
• Recruit eosinophils, neutrophils,
Neutrophil
macrophage
• Mast cell induction & activation (release cytokines, histamine,
lipid mediators)
• Healthy response is self-resolving (active) *****
- disting. asthamatic & healthy response (in severe asthma resolving is compromised - can’t shut it down)
What does Asthma look like?
• Inflammation excessive and not self-resolving (chronic)
• Skewed towards TH2
• Mast cells, eosinophils, neutrophils
• Pathological mediators cause tissue damage and promote AHR (airway hyperresponsiveness)
Asthma Diagnosis requires:
• assessment of clinical symptoms / history (how long?)
• Self-reported breathing difficulty (time of day - typ. feel at night) and
triggers (frequency of “attacks”/symptoms)
• Breaths sounds (ex: crackles)
• measurement of airway function
What is the preferred diagnosis of athma?
spirometry showing REVERSIBLE airway obstruction - measure FEV1/FVC & see if FEV1 changes after a bronchodilator (should show reduced)
& increase in FEV1 after a bronchodilator or after course of controller therapy (should see increase in air after if asthma)
What should we look for on a Methacholine Challenge Test for asthma?
Pc20 v. low (b/c a healthy person can take lots of methacholine & FEV1 on’t drop much)
Measurement of Airway Function: Response to Bronchodilators
Spirometry → inhaled or nebulized bronchodilator (eg. 400g salbutamol) → 15+ min → repeat spirometry (>12% increase in FEV1 is positive result)
we see a 34% improvement in FEV1 - therefore 34% airway R & needs a bronchiodilator or corticosteroid or both
What do we see in fatal asthma?
- lots of ASM that will make airway smaller
- excessive mucous production
- airway wall thickening (fibrosis)
- airway smooth muscle hypertrophy
What does airway remodeling do over time?
improve Pc20 (get higher)
Obstructive Airway Disease: COPD
Chronic Obstructive Pulmonary Disease:
inflammatory lung disease (neutrophilic) that affects airways (bronchitis) and lung parenchyma (emphysema)
• conducting airway wall remodeling, pruning (loss) of terminal
respiratory bronchioles, and alveolar destruction
• Greatly increases lung compliance a significant
component of IRREVERSIBLE airway obstruction
Genetics: Z genotype isn’t good –> means they have v. little of a1-antitrypsin protein circulating in blood which means it doesn’t inhibit endogenous proteins of lung or the ones that neutrophiles release when activated by cigarette smoke
What do we see in Emphysema?
huge air sacs, therefore LESS SA to gas exchange (get more air into lungs but diffusing capacity is compromised b/c no capillary bed)
& protein for elastic fibres is being degraded by endogenous enzymes
Chronic Cigarette Smoking Leads to…
Accelerated Loss of Lung Function
- Alveolar loss is IRREVERSIBLE; preventing damage is paramount
- Smoking cessation can re-establish normal rate of decline in lung function (depends when the person stops smoking)
Cellular Basis of Inflammation & Tissue Repair in COPD
Alveolar Macrophage:
- Primary defense - increased number in smokers
- Phagocytes (deposits, dead cells, bacteria)
- Release cytokines to recruit (IL-8) and activate (TNF) neutrophils
- Secrete MMP-12 metalloelastase to degrade elastin (modulated by endogenous anti-proteases α1 anti-trypsin (A1AT) & Tissue inhibitors of metalloproteinases (TIMPs)
Cellular Basis of Inflammation & Tissue Repair in COPD
Neutrophils (recruited)
• Secondary defence: aggressive phagocytes
• Secrete neutrophil elastase and reactive oxygen
species (ROS)
• Elastin degradation and lung cell death/stress
How is there increased Small Airway Resistance in COPD?
• Mucus production
• Alveolar destruction
• Matrix destruction (aka elastin is destroyed)
• Small airway pruning & collapse
• Increased lung compliance (reduced interdependence)
- easy to inflate lungs, but difficult to come back
cartilage in airways prevent airways from collapsing
What does cartilage in the airways do?
cartilage in airways prevent airways from collapsing
Emphysema: patients breathe at
higher FRC to overcome loss of radial force on airways
• peribronchial pressure becomes positive during forced expiration
• at equal pressure point (EPP) airways collapse
• EPP is more easily reached in emphysema
• Pursed lips breathing helps (pop opens airways)
Chronic Bronchitis:
• Productive cough (disting. b/t asthma & COPD) and wheezing
• Inspiratory & expiratory coarse crackles
• Cardiac: tachycardia common in exacerbations
What do the Pulmonary function tests look like in Chronic Bronchitis?
• reduced expiratory flows and volumes
• FEV1, FVC, and FEV1/FVC reduced
• airway obstruction NOT responsive to pre-bronchodilators (disting. from asthma)
• expiratory F-V curve shows substantial flow limitation
• increase in RV and FRC
• air trapped due to airway obstruction & early airway closure
Emphysema:
• Dyspnea & progressive airway obstruction
• Abnormalities of gas exchange (exercise
intolerance) (b/c losing alveoli)
• Decreased breath sounds intensity
• Tachycardia (exacerbations) & pulmonary
hypertension (b/c taking out alveoli but also pulmonary circulation as tissues break down & therefore increase R b/c capillary bed is disappearing)
• Arterial blood gas: loss of the alveolar
capillaries leads to arterial O2 desaturation
Pulmonary function tests for emphysema
• dynamic airways compression during expiration → reduced FEV1, FVC, and FEV1/FVC (ie. volume they breathe out is less than volume they breath in)
• obstruction NOT responsive to pre-bronchodilators
• flow limitation evident in expiratory F-V curve
• air trapping: increased RV, FRC and TLC
What is a hint that its COPD not asthma?
FVC reduced in severe disease (hyperinflation in
COPD) so need FEV1:FVC to isolate airway function!
What are 2 things to know about Flow-volume loop in emphysema?
- PEF = peak expiratory flow - in a healthy person it peaks in 1 sec (10L/s) then slows down –> indication of elastic recoil in the lungs
- In a person with obstruction - PEF is 2.5L/s & MEF is much lower (in COPD you can breath in, but hard to breath out)
Ways to diagnosis emphysema
- Physical exam: Barrel chest, decreased breath sounds
- Chest X-Ray: can show abnormally large lungs
- Chest CT Scan: can show small pockets of trapped air
- Blood tests for: genetic disease evaluation; arterial blood gas; and, white blood cell count (b/c increase in WBCs is linked to infection)
- Pulmonary function testing
Emphysema vs. Chronic Bronchitis clinical presentation
Emphysema:
- Severe dyspnea
- Cough after dyspnea
- Sputum not excessive
- Less frequent lung infections
- Terminal resp. failure
- Diffusing capacity (DLCO) decreased
Chronic Bronchitis:
- Mild dyspnea
- Cough before dyspnea
- Copious, purulent sputum
- More frequent lung infections
- Repeated resp. insufficiency
- DLCO less affected (b/c its their airways not alveoli thats affected)
COPD Treatment:
• Smoking cessation
• Annual influenza vaccination
• Active lifestyle (don’t want to but it can prolong their life)
• Alleviate dyspnea - pharmacologics
management only b/c COPD is paletive/can’t stop
Pharmacologic Management of COPD
Bronchodilation (airway smooth muscle relaxation) and reduced mucous production:
- Anti-cholinergics
- β2 agonists
- Phosphodiesterase 2 inhibitors
Pharmacologic Management of COPD
Control infection, reduce inflammation:
- Antibiotics
- Anti-inflammatory medications:
• Inhaled corticosteroids, PDE2 inhibitors
• Reduce macrophage/neutrophil content
