Obstructive Lung Disease- Bootcamp Flashcards
Obstructive lung disease occurs as a result of some kind of obstruction to airflow that causes an increase in airway resistance; this causes FEV1 to _ and FVC to _
Obstructive lung disease occurs as a result of some kind of obstruction to airflow that causes an increase in airway resistance; this causes FEV1 to dramatically decrease and FVC to decrease
Obstructive lung disease is associated with a _ FEV1/FVC ratio
Obstructive lung disease is associated with a decreased FEV1/FVC ratio
* Due to the dramatic decrease in FEV1
Three common examples of obstructive lung diseases are _ , _ , and _
Three common examples of obstructive lung diseases are COPD , asthma , and cystic fibrosis
The two “phenotypes” of COPD are _ and _
The two “phenotypes” of COPD are emphysema and chronic bronchitis
Emphysema causes airway obstruction via _ while chronic bronchitis causese airway obstruction via _
Emphysema causes airway obstruction via equal pressure point moving towards the alveoli while chronic bronchitis causese airway obstruction via mucus blocking the airways
Emphysema causes a “dynamic” obstruction; explain
Emphysema –> lung elastic tissue destroyed –> decreased elastance and increase compliance –> equal pressure point moves towards the alveoli –> dynamic airway collapse
Asthma causes obstruction via _
Asthma causes obstruction via bronchoconstriction
* Causing episodic airway obstruction
Cystic fibrosis causes obstruction via _
Cystic fibrosis causes obstruction via thick mucus plugging
Episodic, reversible bronchoconstriction describes _
Episodic, reversible bronchoconstriction describes asthma
Common symptoms of asthma
Asthma symptoms include:
* Wheezing
* Coughing
* Dyspnea
* Hypoxemia
* Asymptomatic between episodes
Asthma bronchoconstriction is caused by _
Asthma bronchoconstriction is caused by airway hyperresponsiveness
Three components of the “atopic triad”
“Atopic triad”
1. Atopic asthma
2. Atopic dermatitis
3. Allergic rhinitis
Common allergens are dust, pets, pollen
Atopic asthma is caused by _ and is mediated by _
Atopic asthma is caused by an identifiable allergen and is mediated by IgE
* It is a Type I Hypersensitivity reaction
* Classically triggered by pets, dust, pollen
Non-atopic asthma is _
Non-atopic asthma has no identifiable allergen
* It usually follows viral infection, stress or exercise
_ is severe asthma that has an acute onset and can be fatal
Status asthmaticus is severe asthma that has an acute onset and can be fatal
NSAIDs can also induce asthma by blocking the _ pathway and upregulating the production of _
NSAIDs can also induce asthma by blocking the COX pathway and upregulating the production of leukotrienes (via the LOX pathway)
Nasal polyps in adults are commonly associated with _
Nasal polyps in adults are commonly associated with NSAID induced asthma
Nasal polyps in children are commonly associated with _
Nasal polyps in children are commonly associated with cystic fibrosis
Atopic asthma pathophysiology
- Antigen enters
- Antigen is presented by APC to Th2 cell
- Th2 cell releases cytokines
- IL-5 recruits eosinophils
- IL-4 and IL-13 stimulates plasma cells to make IgE
- IgE primes the mast cells (IgE binds the mast cell)
- Mast cells are ready to degranulate
- On repeat exposure, the antigen binds IgE and mast cell degranulates
- Release of histamine and leukotrienes –> bronchoconstriction
The early phase of an asthma reaction involves bronchoconstriction caused by _ and _
The early phase of an asthma reaction involves bronchoconstriction caused by histamines and leukotrienes
In the late stage of an asthma reaction, _ cells are recruited to _
In the late stage of an asthma reaction, eosinophils are recruited to release major basic protein –> inflammation and mucus production
Asthma can be diagnosed with spirometry that shows a _ FEV1/FVC
Asthma can be diagnosed with spirometry that shows a decreased FEV1/FVC
In order to diagnose asthma using spirometry, we often have to induce an asthma episode with administration of _
In order to diagnose asthma using spirometry, we often have to induce an asthma episode with administration of methacholine
* Methacholine challenge causes bronchoconstriction
Healthy individuals spend about twice as long expiring as they do inspiring; asthmatic patients might spend _ time in expiration
Healthy individuals spend about twice as long expiring as they do inspiring; asthmatic patients might spend four times more time in expiration
* I/E goes from 1/2 –> 1/4
_ are eosinophil granules found in the sputum that can help to diagnose asthma
Charcot-Leyden crystals are eosinophil granules found in the sputum that can help to diagnose asthma
Curschmann spirals are _ and are also found in the sputum of patients with asthma
Curschmann spirals are whorled mucus plugs with epithelial casts and are also found in the sputum of patients with asthma
Cromolyn sodium treats asthma by _
Cromolyn sodium treats asthma by stabilizing mast cells
Meplizumab, Reslizumab, Benralizumab treat asthma via _ mechanism
Meplizumab, Reslizumab, Benralizumab are IL-5 and IL-5 receptor antagonists
* Decrease eosinophil activation and recruitment
Inhaled corticosteroids help asthma patients by _
Inhaled corticosteroids help asthma patients by suppressing cytokine production and also causing eosinophil apoptosis
* Fluticasone, Budesonide, Beclomethasone
Omalizumab is an asthma drug that is _
Omalizumab is an asthma drug that is an anti-IgE antibody
Lukast drugs are _ drugs
Lukast drugs are anti-leukotriene receptor drugs
Zileuton is a _ drug
Zileuton is an anti-lipoxyganase drug
Albuterol is a _ type drug
Albuterol is a short-acting B2 agonist (SABA) that induces bronchodilation
_ and _ are two long acting B2 agonists (LABAs)
Salmeterol and Formoterol are two long acting B2 agonists (LABAs) that cause bronchodilation
Ipratropium is a medication used in asthma that is _
Ipratropium is a medication used in asthma that is anti-muscarinic –> bronchodilation
Theophylline is an asthma drug that is a _
Theophylline is an asthma drug that is a PDE inhibitor –> increases cAMP –> bronchodilation
_ is a common medication choice for acute exacerbations of asthma
Albuterol is a common medication choice for acute exacerbations of asthma
_ + _ is a common combination drug used for treatment of persistent asthma
Corticosteroid + LABA is a common combination drug used for treatment of persistent asthma
Why can LABAs not be given as a monotherapy?
LABAs over time will cause downregulation of B2 receptors; therefore they must be combined with corticosteroids which upregulate B2 receptors
In cases of resistant asthma in which patients have continued high IgE levels, _ can be given
In cases of resistant asthma in which patients have continued high IgE levels, Omalizumab can be given
_ is an asthma medication that can cause oral candidiasis if not rinsed after use
Inhaled corticosteroids are an asthma medication that can cause oral candidiasis if not rinsed after use
_ is an asthma drug that can have a caffeine-like effect due to adenosine blockade
Theophylline is an asthma drug that can have a caffeine-like effect due to adenosine blockade
_ is an irreversible dilation and destruction of the airways; it is most commonly caused by cystic fibrosis
Bronchiectasis is an irreversible dilation and destruction of the airways; it is most commonly caused by cystic fibrosis
Patients with obstructive disease like COPD take _ breaths
Patients with obstructive disease like COPD take slow, deep breaths
* They try to hold the airways open by taking deep breaths
* They decrease the turbulence and airway resistance by breathing slowly
* They also may purse their lips on expiration to create back-pressure
Patients with restrictive lung disease will take _ breaths
Patients with restrictive lung disease will take rapid, shallow breaths
* They attempt to decrease the work of breathing by decreasing lung volume and decreasing elastic recoil force of the lungs
(Emphysema/ Chronic bronchitis) causes patients to experience the chronic dyspnea; (Emphysema/ Chronic bronchitis) causes the persistent coughing
Emphysema causes patients to experience the chronic dyspnea; chronic bronchitis causes the persistent coughing
COPD is a common disease that commonly presents in _ individuals
COPD is a common disease that commonly presents in smokers
* Other risk factors include air pollution exposure, occupational exposure, multiple chronic infections
COPD in a young individual, who does not smoke may be due to _
COPD in a young individual, who does not smoke may be due to genetic cause like A1AT deficiency
_ is an antiprotease that keeps elastase in check to prevent degradation of alveolar tissue
a1-antitrypsin is an antiprotease that keeps elastase in check to prevent degradation of alveolar tissue
* Some individuals have a genetic mutation that causes A1AT to misfold and never leave the hepatocyte ER
Aside from affecting the lungs, A1AT deficiency can also affect the _
Aside from affecting the lungs, A1AT deficiency can also affect the liver
* Patients might present with liver failure due to accumulated A1AT in the hepatocyte ER
A1AT deficiency tends to cause _ type emphysema
A1AT deficiency tends to cause panacinar emphysema
* Patients will normally be diagnosed in 40s-50s
* Effects will be more severe in patients who smoke
Pathogenesis of COPD (specifically chronic bronchitis)
Airways become inflamed (ie cigarette smoke) –> neutrophils migrate to the area –> release cytokines + ROS –> ROS are intended to kill bacteria but when inflammation persists they can cause damage to the inflamed area –> increase mucus production (upregulate goblet cells) –> airway obstruction
Two major histopathologic changes are seeen in chronic bronchitis _ and _
Two major histopathologic changes are seen in chronic bronchitis goblet cell hyperplasia and squamous metaplasia
Constant bronchiolar injury induces ciliated pseudostratified columnar cells to be replaced with _
Constant bronchiolar injury induces ciliated pseudostratified columnar cells to be replaced with squamous epithelium
The consequence of squamous metaplasia is that the loss of cilia causes _
The consequence of squamous metaplasia is that the loss of cilia causes increased infection risk
Proteases are mostly made by _ cells
Proteases are mostly made by neutrophils and macrophages
Antiproteases are secreted by _ cells to keep proteases in check
Antiproteases are secreted by resident epithelial cells to keep proteases in check
The destruction of septae in emphysema can lead to enlarged areas of dilated lung sacs called _
The destruction of septae in emphysema can lead to enlarged areas of dilated lung sacs called blebs or bullae
Centriacinar emphysema affects _
Centriacinar emphysema affects center of the acini (respiratory bronchi)
* Associated with smoking
* Most common type
Panacinar emphysema affects _
Panacinar emphysema affects the entire acinus
* It is less common and associated with A1AT deficiency
Paraseptal empysema affects _
Paraseptal empysema affects the periphery of the acinus
* Associated with pulmonary scarring
_ emphysema is most likely to cause a spontaneous pneumothorax due to destruction just beneath the pleura
Paraseptal emphysema is most likely to cause a spontaneous pneumothorax due to destruction just beneath the pleura
Three consequences of COPD
- Hypercapnia
- Bronchiectasis
- Pulmonary hypertension
Long term hypoxia in COPD induces the production of _ and _
Long term hypoxia in COPD induces the production of 2,3-BPG and EPO
* EPO is a hormone made by the kidneys that stimulates the bone marrow to make more RBCs –> polycythemia
The Reid index is the proportion of _ to _
The Reid index is the proportion of mucus glands/ mucosa + submucosa
In chronic bronchitis, the Reid index will be greater than _
In chronic bronchitis, the Reid index will be greater than 50%
What are the classic lab values expected in chronic bronchitis?
PaO2
PaCO2
pH
HCO3-
PaO2: decreased
PaCO2: increased
pH: decreased (< 7.35)
HCO3-: increased
Why is oxygen therapy dangerous for COPD patients?
COPD patients (especially with chronic bronchitis) have hypercapnia –> over time their central/medullary chemoreceptors stop responding to the high CO2 levels –> they then rely entirely on their peripheral chemoreceptors to respond to low O2 –> if oxygen is delivered to COPD patient then hypoxic drive to breathe will be decreased –> can cause patient to be even more hypercapnic
DLCO is decreased in (chronic bronchitis/ emphysema)
DLCO is decreased in emphysema
* Emphysema affects our diffusing capacity because it degrades our alevoli and decreases surface area
* Chronic bronchitis is a problem of the bronchi, it does not affect the alveoli
Cyanosis is associated with (chronic bronchitis/ emphysema)
Cyanosis is associated with chronic bronchitis
* Emphysema is not usually associated with cyanosis- there is destruction of both alveoli and capillaries so there is not much of a V/Q mismatch
Explain the pathogenesis of emphysema as a result of cigarette smoking
Smoke –> recruits neutrophils –> neutrophils release protease (elastase) –> elastase degrades around the area where smoke is inhaled which is central, in the respiratory bronchioles of the upper lobes
Cigarette smoking tends to cause _ emphysema in the _ lobes
Cigarette smoking tends to cause centriacinar emphysema in the upper lobes
A1AT deficiency tends to cause _ emphysema in the _ lobes
A1AT deficiency tends to cause panacinar emphysema in the lower lobes
Cystic fibrosis has a _ inheritance pattern
Cystic fibrosis has an autosomal recessive inheritance pattern
Cystic fibrosis is a mutation in the _ protein; it is caused by a _ deletion
Cystic fibrosis is a mutation in the CFTR protein; it is caused by a Phe508del
* CFTR encodes ATP-gated Cl- channel
* The mutated CFTR channel is misfolded and improperly trafficked to the cell membrane
In the GI tract + lungs, Cl- should be (reabsorbed/ secreted) through the CFTR channel in normal individuals; in cystic fibrosis _ occurs
In the GI tract + lungs, Cl- should be secreted through the CFTR channel in normal individuals; in cystic fibrosis Cl- gets trapped inside the cells –> Na+ reabsorption –> H2O reabsorption
* We get thick and dehydrated mucus in the lumen
In the skin, Cl- should be (reabsorbed/secreted) through the CFTR channel; however, in CF _ occurs
In the skin, Cl- should be reabsorbed through the CFTR channel; however, in CF the Cl- builds up in the sweat –> Na+ and H2O will also be lossed in the sweat
What are the consequences of cystic fibrosis?
Thick mucus in the lungs –> mucus plugging –> hyperinflated lungs with productive cough + recurrent pulmonary infections
The most common infection in young CF patients is _
The most common infection in young CF patients is S. aureus
The most common infection in adults with CF is _
The most common infection in adults with CF is P. aeruginosa
* The thick mucus facilitates the formation of biofilms
Bronchiectasis is most commonly caused by _
Bronchiectasis is most commonly caused by CF
How does CF affect the pancreas and GI system?
Thick mucus in the pancreatic and bile ducts –> decreased pancreatic and biliary secretions –> decreased fat soluble absorption –> pancreatitis, steatorrhea, diabetes
Thick mucus in the stool can cause _ in infants
Thick mucus in the stool can cause meconium ileus in infants
* Thick/sticky meconium –> inspissated mass –> bowel obstruction
How does CF normally affect fertility?
Males often have an absent vas deferens –> sterile
Women may have thick cervical mucus making them subfertile
_ CF drug improves protein misfolding and trafficking while _ drug enhances Cl- flux through the channel
Lumacaftor CF drug improves protein misfolding and trafficking while Ivacaftor drug enhances Cl- flux through the channel
