case 5: COPD Flashcards
1
Q
Lab Test Results
A
- Pulmonary function tests – spirometry
– Diffusing (diffusion) capacity (DL) = 16.0 (ml/min/mmHg) (67%
of predicted)
– FEV1 = 45% of normal, No change in FEV1 with bronchodilator
– decrease FVC, (FEV1/FVC) < 0.7 - decrease Vmax
- A sputum sample showed many neutrophils together with
cellular debris
– Culture of sputum showed positive Streptococcus species - Echocardiogram – enlarged right ventricle
2
Q
CXR Results
A
Chest radiographs – hyperinflated lungs; flattened diaphragms
3
Q
Diagnosis
A
- Chronic obstructive pulmonary diseases (COPD) associated
with emphysema, bronchitis, asthma - COPD, also known as chronic obstructive lung disease
(COLD), chronic obstructive airway disease (COAD)
4
Q
COPD – Introduction
A
- Symptoms – any patient who has dyspnea (shortness of
breath, progressive, persistent and characteristically worse
with exercise), chronic cough or sputum production, plus: - A history of exposure to risk factors for COPD:
– Tobacco (cigarette smoking)
– Occupational dusts (organic & inorganic)
– Indoor air pollution from heating & cooking
– Outdoor air pollution - Usually present in fifth decade of life, with dyspnea (initially
only with exertion) or acute chest illness - Spirometry is required to make the diagnosis
5
Q
Structure of Respiratory System
A
- Airway passages
– Conducting zone and respiratory zone - Conducting zone
– Outside the lungs – nasal passage ->
pharynx -> epiglottis -> larynx (glottis)
– Inside the lungs – trachea (1) ->
bronchus (2 branches) -> bronchiole ->
… -> terminal bronchiole
– Functions of conducting zone –
passage of air, warming, humidification,
and filtration - Respiratory zone
– Respiratory bronchiole -> … -> alveoli
– Functions of respiratory zone –
passage of air, gas exchange
6
Q
The Alveoli
A
- Alveoli
– Total # – ~300 x 106
– .25 - .5 mm in diameter
– Total area – 60 - 80 m2 - Alveolar wall
– Type I alveolar cells – the
major lining cells, accounts
for 95-97% of total surface
area
– Type II alveolar cells –
production of surfactants
– Air-blood barrier – ~0.3 micro m
7
Q
Nature Properties of Lungs & Chest Wall
A
- The lung can be viewed as a passive (no contracting or relaxing), elastic container (can recoil inward)
- The pleural space (air sealed) contains only a film of fluid, so lungs normally remain in contact with the chest walls
- The lung tends to recoil inward and the
chest wall outward - These recoil forces in opposite directions
create a negative (sub-atmospheric)
pleural pressure (always negative) - Lungs expand and contract along with the
thoracic cavity
rib cage can recoil inward
mediasternum is a protection mechanism where if there is a fracture it can protect one lobe and not the other
8
Q
Thoracic Cavity
A
- Diaphragm – separates
thoracic & abdominal cavities - Pleural (intra-pleural) space (air sealed)
– Thin fluid layer between
visceral pleura covering
lungs (visceral) and parietal
pleura lining thoracic cavity
walls
– Air-sealed space - Thoracic cavity surrounded by
rib cage (chest wall) and the
respiratory muscles
9
Q
Respiratory Muscles & Ventilation
A
- Respiratory muscles
– Inspiratory muscles – diaphragm, external
intercostals, scaleneus, sternomastoids and
others
– Expiratory muscles – internal intercostals,
abdominal muscles (oblique, rectus &
transverses), and diaphragm - During inspiration
– Contraction of inspiratory muscles -> increase vertical & horizontal distances of thoracic cavity -> increase volume of thoracic cavity - During quiet expiration
– Relaxation of inspiratory muscles -> decrease vertical & horizontal distances of thoracic cavity -> decrease volume of thoracic cavity - During active (forced) expiration, contracts
expiratory muscles -> accelerate exhalation
10
Q
Sequential Events during Inspiration
A
- Inspiration is an active process (active contraction)
- Mechanics of breathing – interplays of (1)
chest (thoracic cavity, rib cage), (2) pleural
space and (3) alveolar space (lung volume)
– At the end of quiet expiration (FRC, Patm =
Palv) – neural input -> contraction of
inspiratory m. -> increase vertical & horizontal
distance of chest -> increase chest vol
– -> chest “pulls” on pleura -> increase pleural vol -> decrease intra-pleural P (Ppl, more negative) -> pulls lungs to expand more
– -> increase lung vol -> decrease Palv (intra-pulmonary P) -> Palv < Patm -> generates P gradient between atmospheric (originally at 0) (Patm > Palv) -> air flows into lungs -> Palv increase -> until Palv = Patm -> airflow ceases (the end of inspiration) - volume and pressure inversely related
- if pleural pressure is 0 then collapse
- pleural pressure more negative it opens alveolar wall
- increase alveolar space then alveolar pressure decrease/become negative relative to atmosphere
when chest wall expands, pleural space air sealed, there’s an increase in pleural space and there decrease pressure
11
Q
Sequential Events during Expiration
A
- Quiet expiration is a passive process (relax expiratory muscles) (with copd you have to contract expiratory muscle to get air out)
– Can you deduce the pressure and vol changes in the chest, pleural space and alveolar space? - During active (forced) expiration,
expiratory muscles contract -> accelerate exhalation - Intra-pleural P = -4 to -5 mmHg at
the end of quiet expiration (beginning of next inspiration) (FRC)
12
Q
Lung Volumes and Capacities
A
- 4 primary lung volumes – tidal volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV) and residual volume (RV)
- 4 lung capacities – inspiratory capacity (IC), functional residual capacity (FRC) (ERV + RV), vital capacity (VC) (IRV + TV + ERV) and total lung capacity (TLC) (all 4 vol together)
13
Q
Measurement of Lung Volumes
A
- Lung volumes, capacities & air flow rates
indicate clinical pulmonary functions - Measurement of lung vol – spirometry
– Patient inhales -> air into lungs from spirometer, pen deflects upward
– Patient exhales -> pen deflects downwards
– Limitations of spirometry – cannot measure RV & FRC (RV+ERV) - Dilution method – measure RV & FRC
– Use of radioactive helium (inert gas)
– Takes some breaths to reach equilibrium
– C1 x V1 = C2 x (V1 + V2)
14
Q
Measurement of FVC & FEV1
A
- EFV1 – forced expiratory volume in 1 second
– Is the volume of air that can forcibly be blown out in one second, after full inspiration - FVC (forced vital capacity)
– The patient is asked to take the deepest breath they can
– -> then exhale into the sensor as hard as possible (6-10”)
– The max volume patient expires is FVC
15
Q
Respiration and Pressure Gradient capillaries
A
- How do we get O2 into the body
and CO2 out of the body?
(Ventilation)
– Ventilation results from pressure
differences (gradient) induced by
changes in lung volumes
– Pressure (P) gradient – results in
net gas flow & diffusion from high
P to low P
– For PO2 – alveolar space > blood
plasma > interstitial fluid > cytosol
> mitochondria
– For PCO2 – mitochondria > cytosol
> interstitial fluid > blood plasma >
alveoli
16
Q
Surface Area for Diffusion
A
- Respiratory membrane
– Large surface area, extensive
branching & clusters of alveoli
– Thin membrane, single layer of
epithelial cells, single layer of
endothelial cells, fused basement
membranes
17
Q
Factors that Create Gas Diffusion
A
- Molecular basis of gas diffusion
– Net movement follows a pressure gradient - Diffusion barriers
– Exchange of O2 and CO2 in the lung takes
place in 3 separate phases (air, solid, and
liquid), each involving diffusion
– A fluid lining, alveolar membrane, an
epithelial basement membrane, interstitium,
a capillary basement membrane, capillary
endothelial membrane, plasma, and RBC
cell membrane - Only dissolved gas in fluid accounts for
partial P of that gas
18
Q
COPD – Definition
A
- (Global Initiative for Chronic Obstructive Lung Disease,
GOLD) – a disease state characterized by airflow limitation
that:
– is not fully reversible
– is usually progressive
– is associated with an abnormal chronic inflammatory response
of the lungs to noxious particles or gases - A disease state characterized by the presence of airflow
obstruction due to chronic bronchitis and/or emphysema; the
airflow obstruction is generally progressive, may be
accompanied by airflow hyperactivity, and may be viewed as
partially reversible, characterized by chronically poor airflow
and typically worsened over time
19
Q
COPD – Prevalence
A
- The only one out of the top 10 causes of death with increasing prevalence
– Prevalence increases with age - Increase more marked in women
- Worldwide, COPD affects 329 million people (~ 5% of the population). In 2012, it killed >3 million people
- Worldwide, the number of deaths is projected to increase due to higher smoking rates and an aging population
- Resulted in an estimated economic cost of $2.1 trillion in 2012
20
Q
Principle of Physical Examination
A
- Physical exam cannot diagnose early disease
- Airflow obstruction
– Wheezing (why?) when theres obstruction , airflow going in and out become turbulent rather than laminay, causing more energy
– Prolongation of forced expiratory time (inspiration vs. expiration) expiration takes longer time to get air out bc after inspired air into lung, enough alveolar space is compressed of bronchiole, diameter is too narrow, further compressed by air, prolongation of forced expiratory time - Lung hyperinflation
– Low diaphragmatic position
– Increased resonance to percussion (why?) there will be some emphysema and air gets trapped in lung without surrounding alveolar wall, there’s less resistance of alveolar wall
– Decreased intensity of heart and breath sounds (why?) it’s blocked by air, can’t be transmitted by solid tissue - Severe disease
– Pursed-lip breathing (why?) air flow more stable, to get air into and out easier
– Use of accessory respiratory muscles (why?) expiration is more difficult because of airway limitation/obstruction. accessory muscle needed to help get air into and out of lung to breathe
– Retraction of intercostal space (why?) contraction is harder, vacuum space causes negative pressure so even the muscle is retracted, so intercostal space
21
Q
Airway Limitation – Confirmation
A
- All persons > 45 yr-old with chronic cough & sputum, with a history of exposure to risk factors, with or without
dyspnea should be tested for airflow limitation - Spirometry – performed after inhaling a short-acting bronchodilator to minimize variability
- FEV1/FVC < 0.70 (normal = 0.8) confirms airflow limitation
22
Q
Assessment of COPD Severity
A
- Classification of severity in patients with FEV1/FVC < 0.70
– GOLD 1 – mild, FEV1 > 80% predicted
– GOLD 2 – moderate, 50% < FEV1 < 80% predicted
– GOLD 3 – severe, 30% < FEV1 < 50% predicted
– GOLD 4 – very severe FEV1 < 30% predicted - Predicted value – defined as FEV1 of the patient divided by the average FEV1 in% in the population for any person of
similar age, sex and body composition
– To avoid over-diagnosis of COPD in the elderly
23
Q
Types of COPD
A
- COPD – formed by a mixture of 3 separate disease processes (chronic bronchitis, emphysema and a lesser extent of asthma)
with various combinations - Chronic bronchitis
– Cough productive of sputum for at least 3 months over 2 consecutive years
– Excessive mucus production with airway obstruction - Emphysema – gradual destruction of alveolar wall & pulmonary capillaries -> decrease ability to oxygenate blood -> decrease PaO2
- Asthma – spasms in the bronchi of the lungs, causing difficulty in breathing (usually results from allergy or other hypersensitivities)
24
Q
Chronic bronchitis
A
Chronic productive cough for 3 consecutive months for 2 consecutive years
25
Q
Emphysema
A
Abnormal enlargement of airspaces distal to terminal bronchioles & destruction of alveolar walls, air trapped in the lung cannot be forced out, volume increases?
26
Q
COPD Subtype – Chronic Bronchitis
A
- Mucus gland hypertrophy
- Smooth muscle hypertrophy
- Goblet (mucous) cell hyperplasia
- Inflammatory cell infiltration
- Excessive mucus
- Squamous metaplasia
- 1-6 -> thickening of wall -> airflow limitation -> COPD
27
Q
COPD – Pathogenesis
A
- Smoking, pollutants, or decrease α1-antitrypsin (A1AT) decrease inflammation:
– 1. Inflammation in airway: - increase Airway mucus -> luminal plugs -> increase airway resistance
- Airway tissue fibrosis -> increase airway resistance
- Chronic bronchitis
– 2. Inflammation in alveolar wall (parenchyma) - Inflammation -> neutrophil & macrophage infiltration
- -> increase elastase secretion -> degrade elastic fibers
- -> destruction (breakdown of alveolar wall)
- -> emphysema
- -> Airflow limitation
macrophages moving along alveolar sac to remove unwanted particles
28
Q
COPD – Cellular Mechanisms
A
- Chronic bronchitis – “blue bloater”, higher BMI
– major increase Mucus production with airway obstruction -> hypercapnia (increase PaCO2) & hypoxemia (decrease PaO2) -> cyanosis
– increase Edema, more normal diffusion capacity, less hyperinflation - Emphysema – “pink puffer”, lower BMI
– Emphysema sufferers may hyperventilate -> maintain blood PO2 -> do not appear cyanotic
– Hyperinflation with flattened diaphragm, reduced diffusion capacity - cannot put air out because lack alveolar recoil to push it out
29
Q
The diffusion capacity of this patient is reduced
(diffusing capacity = 16.0 ml/min/mmHg, or 67% of predicted), why?
A
- For this patient:
– Alveolar tissue is destroyed due to chronic inflammation (emphysema)
– -> decrease Surface area for gas exchange -> decrease diffusion capacity (67% of normal)
30
Q
Diffusion Rates & Diffusion Capacity
A
- Diffusion rate (Fick’s Law )
– The net diffusion rate of a gas
across a membrane over time
– Is proportional to the surface area of
the membrane, proportional to the P
gradient and inversely proportional
to the thickness of the membrane
– V̇̇ gas = (A/T) * D * (P1 - P2) - A = tissue surface area; T = tissue thickness (< 0.5 micro m)
- D = diffusion constant of a gas
- P1-P2 = P gradient across the tissue barriers
- D inversely related (solubility of gas/square root m.w.)
- Diffusing capacity of lungs – DL = (A/T) . (P1-P2) (ml/min/mm Hg)
– DL varies among individuals
31
Q
- How might the hyperinflated lungs, flattened diaphragms occur in
this patient? - What would happen to the lungs and chest wall if there is a hole (such as
rib fracture) that opens up the rib cage of chest wall? why barrel shaped
A
- The pleural sac between the chest
wall and lungs is no longer airtight
-> the lung collapsed and chest
wall becomes barrel-shaped. But
why? - Lung tissues lost the tug of war -> increase CL -> hyper-expansion of lungs
-> hyperresonance & flat diaphragm - In patient with emphysema, elastic fibers are degraded by
proteases (elastase, cathepsins etc.) -> decrease elastance -> lung tissues
fail to recoil back after expansion by inspiration
32
Q
when Pleural P = 0 mm Hg
A
When Pleural P = atmospheric P (i.e. no longer negative) ->
the pulling force disappears -> lung recoil inward (collapsed)
and chest wall recoil outward (barrel-shaped chest)
33
Q
Lungs & Chest Wall – Tug-of-War
A
- The lung tissues and chest wall are always in a tug-of-war,
with the pleural (intrapleural) space as the interface
34
Q
Interaction between Lungs & Chest Wall
A
- The nature property of lungs is to recoil inward:
- Elastic fibers in alveolar wall
- Surface tension in alveoli
- The nature property of the chest wall is to recoil outward
- These opposing recoil forces on each side of the pleural sac
create a negative (subatmospheric) pleural P ( -4 - -5 mm Hg)
35
Q
Factors Affecting Ventilation – Compliance
A
- Compliance
– Compliance is the expansibility of the lungs; a measure of the “ease” with which the lungs can expand
– Lung compliance – the change of lung volume per unit change of pressure
– CL = change in VL / change in PL
– CL = Lung compliance
– VL = Change in lung volume
– PL = Change in transpulmonary pressure
– The greater the compliance is, the easier the lungs will expand - Lung elastance = 1/CL ; measures how well the lung tissue can bounce back after expansion
36
Q
About Carbon Monoxide (CO)
A
- Hb is composed of 4 subunits as 2
identical dimers, (α β)1 and (α β)2. - Normally 1 O2 binds to 1 heme
molecule -> 1 Hb binds to 4 O2 - CO binds to Hb at the same sites
as O2, but ~220 x firmer
– -> CO cannot be unloaded from Hb
easily
– -> decrease [Hb] available to bind O2 - Patients with CO poisoning has reduced [Hb] available for O2 transport
– -> Gradual suffocation (CO poisoning)
37
Q
Why is the plasma level of carboxyhemoglobin (HbCO)
increased in this patient?
A
- Carbon monoxide (CO) is
produced by burning any
carbon-based substance. - When tobacco is burned the
smoke is inhaled into lungs ->
CO is rapidly absorbed into
blood - -> Formation of Hb-CO
- -> increase [Hb-CO] in the blood -> decrease
[Hb-O2]
38
Q
COPD – Effects of Smoking Cessation
A
- Smoking accelerated aging of the lung
- Smoking cessation slows lung function decline in mild COPD
39
Q
- Why is the plasma level of PCO2 increased and PO2 decreased
in this patient? - Why is the plasma Hb-O2 saturation rate decreased in this
patient?
A
emphysema -> decrease surface area -> decrease diffusion
capacity -> decrease total O2 & CO2 can be diffused through gas exchange barriers -> decrease PO2 & increase PCO2
* decrease PO2 -> decrease Hb-O2 saturation rate (90%)
* 5% HbCO also reduces the availability of Hb to bind to O2
40
Q
Physical Exam
A
- T – 37°C; HR – 90/min; RR – 30/min; BP – 160/80 mmHg;
BMI – 19; O2 saturation rate – 90% - Prominent jugular venous distention
- Accessory muscles of breathing in use
- Prolonged pursed lip expiration with expiratory wheezes
- Chest:
– Increased A-P diameter, barrel chest
– Hyperresonant lung sounds noted on percussion
– Diaphragms low (CXR) - Extremities – peripheral edema
41
Q
This COPD patient’s symptoms include prominent jugular
venous distention, peripheral edema and enlarged right
ventricle. What is the main connection with these symptoms?
A
- Hypoxia – low PO2 in the alveoli caused by high altitude
(atmospheric hypoxia ) or diseases (COPD, pulmonary fibrosis,
embolism in the lung blood vessels, sleep apnea etc.) - Pulmonary blood vessels respond to low PO2 with vasoconstriction
(hypoxic vasoconstriction) - Systemic hypoxic vasodilation, why? hypoxic condition in peripheral tissue in systemic circulation means increase in metabolic activity, skeletal muscle
- Pulmonary hypoxic vasoconstriction, why?
– decrease PAO2 -> interpreted as insufficient tissue perfusion ->
vasoconstriction -> decrease blood flow
– Rationale – shunts pulmonary blood away from poorly ventilated areas -> diverts more blood to well-ventilated areas - When the all lungs encounter low PO2 -> general hypoxic vasoconstriction -> increase R (PVR) -> (Q = P/R -> P = Q*R) -> pulmonary hypertension
42
Q
Fluid Movement in Pulmonary Capillaries
A
- Interactions between the hydrostatic P and colloid osmotic P
- Normally the filtration P (+1 mmHg) causes a slight continual flow of fluid from pulmonary capillaries to interstitial space
- Pulmonary lymphatics normally keep a slight “-” P in interstitium -> absorb fluid and carry away -> maintain dryness in alveolar wall &
alveolar space
43
Q
Pulmonary Edema
A
- Fluid accumulation in interstitium of alveolar wall -> fluid accumulation in alveolar space -> increase thickness of diffusion barrier ->
decrease diffusion capacity -> dyspnea, air hunger - Pulmonary edema may be caused by high altitude, heart diseases or damage to pulmonary capillary membrane (infection)
- Treatment – diuretics, aspiration, heart medications, surgery etc.
44
Q
Pulmonary Hypertension
A
- Result from the combined effects of pulmonary hypoxic vasoconstriction, pulmonary artery remodeling and thickening
(narrowing vascular lumen) , inflammation and loss of capillaries in severe emphysema - Pulmonary hypertension
– Congestion on the right heart (ventricle then atrium) (more difficult for right heart to pump blood) -> jugular vein distention, hepatomegaly, low extremity edema
– Pulmonary edema -> dyspnea - Untreated cases -> chronic high P in right ventricle -> Rt ventricle hypertrophy -> Rt ventricle failure (cor pulmonale)
45
Q
Another Cause of COPD – A1AD
A
- α1 Antitrypsin deficiency (A1AD) – defective production of α1 antitrypsin (accounts for 1-2% of total COPD case)
– -> decrease A1AT activity in blood (from liver) and lungs
– -> decrease Protective activity against proteolytic enzymes (elastase etc.)
– -> Breakdown of alveolar wall (emphysema) - produced by liver
46
Q
risk factors for copd
A
- cigarette smoke
- occupational dust and chemicals
- environmental tobacco smoke (ETS)
- indoor and outdoor air pollution
- genes (A1AD)
- infections
- socio-economic status- nutrition
- aging populations
47
Q
More about Cigarette Smoking
A
- 55-75% of COPD patients are current or former smokers
- 1.3 billion of smokers worldwide, expect to increase substantially
- Smoking is highly addictive – cessation in 12-35% only
- As more women have become smokers, more women than men are now diagnosed with COPD.
- COPD tends to occur at a younger age in women and at a lower threshold of exposure to cigarette smoke.
- Women with COPD also report more accompanying symptoms of ill-health and poorer quality of life than men.
48
Q
Occupational & Household Pollutants
A
- If all patients stop smoking now, COPD rates would still increase next 20 years
– Due to air pollution – occupational exposure - 35% of people with COPD in countries with low-middle income developed the disease after indoor exposure (biomass fuels)
- 19% of COPD cases in US related to workplace exposure
– Ozone, sulfur dioxide, nitrogen dioxide, carbon monoxide
– Particulate matter (PM) 10 – < 10 μm
49
Q
Sympathetic Adrenergic Receptors
A
- Mechanisms of action
– α 1-, α 2 R activation - Activation of α 1 R -> increase [Ca2+]cytosol -> smooth muscle contraction -> vasoconstriction at certain viscera
- Activation of α2 R – inhibits NE release in a form of negative feedback
– β 1-, β 2 R activation -> increase [cAMP]cytosol - β 1 R -> increase heart rate & contractility
- β 2 R -> smooth muscle relaxation (bronchodilation; vasodilation at skeletal muscles)
50
Q
COPD Medications
A
- Beta2-agonists (why?)
- Anticholinergics (why?)
– Block parasympathetic activity in
the large & medium-sized airways
(↓ airway smooth muscle
constriction) → improve expiratory
flow limitation - Inhaled or systemic corticosteroids
– anti-inflammation
– Combination of beta2-agonists +
corticosteroids in one inhaler - Phosphodiesterase (PDE4)
inhibitors – bronchodilation,
vasodilation & anti-inflammation - cAMP, cGMP → ↓ Ca+2 influx
→ bronchodilation - PDE4 → ↓ (cAMP & cGMP)
- PDE4 inhibitors – ↑ (cAMP &
cGMP) → ↑ bronchodilation, ↑
vasodilation & ↑ anti-
inflammation
