Obstructive/Restrictive Disease- Lecture Flashcards
Draw the volume-flow loop in obstructive lung disease
Draw the volume-flow loop in restrictive lung disease
_ is characterized by airway inflammation, hyperresponsiveness, and reversible airflow obstruction
Asthma is characterized by airway inflammation, hyperresponsiveness, and reversible airflow obstruction
What happens during an asthma exacerbation?
- Bronchoconstriction
- Mucosal inflammation
- Increased mucus production
Patient has a decreased FEV1/FVC which is normalized after bronchodilation
This is characteristic of asthma- it is reversible whereas COPD is not
The asthma phenotypes that are associated with high Th2 include:
High Th2:
* Allergic asthma
* Eosinophilic asthma
* Exercise-induced asthma
* Aspirin induced asthma
The asthma phenotypes that are not associated with Th2 (non-Th2) include:
Non-Th2:
* Neutrophilic asthma
* Obesity associated
* Infection-induced asthma
IL-4 is a type 2 cytokine that causes _
IL-4 is a type 2 cytokine that causes production of IgE
IL-5 is a type 2 cytokine that causes
IL-5 is a type 2 cytokine that attracts eosinophils to the bronchial wall
IL-9 is a type 2 cytokine that
IL- 9 is a type 2 cytokine that heightens the Th2 response
IL-13 is a type 2 cytokine that causes
IL-13 is a type 2 cytokine that promotes mucus production
Two short acting beta agonists used for asthma include _ and _
Two short acting beta agonists used for asthma include albuterol and epinephrine
Three long acting beta agonists used for asthma:
- Salmeterol
- Formoterol
- Indacaterol
_ is a short acting muscarinic antagonist
Ipratropium is a short acting muscarinic antagonist
Three long acting muscarinic antagonists include:
- Tiotropium
- Aclidinium
- Umeclidinium
Theophylline is another drug that can be used as a bronchodilator that has _ mechanism
Theophylline is another drug that can be used as a bronchodilator that is a phoshodiesterase4 inhibitor
The muscarinic receptor in the lungs that can be antagonized to treat asthma is specifically the _ receptor, which is a _ g protein
The muscarinic receptor in the lungs that can be antagonized to treat asthma is specifically the M3 receptor, which is Gq coupled receptor
Both beta receptors (beta1 and beta2) are _ G protein coupled
Both beta receptors (beta1 and beta2) are Gs –> adenylyl cyclase –> cAMP
The a2 and M2 receptors are coupled to _ G proteins
The a2 and M2 receptors are coupled to Gi –> inhibits adenylyl cyclase
a1, M1, M3 are _ G protein coupled
a1, M1, M3 are Gq coupled –> PLC –> Ca2+
cAMP in the bronchiole smooth muscle cell leads to (bronchodilation/ bronchoconstriction)
cAMP in the bronchiole smooth muscle cell leads to bronchodilation
Adenosine binds to bronchiole smooth muscle cell and induces _
Adenosine binds to bronchiole smooth muscle cell and induces bronchoconstriction
Theophylline is a _ inhibitor (although with poor sensitivity) and it works by _ and _
Theophylline is a phophodiesterase4 inhibitor (although with poor sensitivity) and it works by blocking adenosine binding and breaking down PDE4 to increase cAMP levels
PDE4 normally _ cAMP
PDE4 normally breaks down cAMP
* Giving a drug that inhibits this therefore rises cAMP levels
* Can induce bronchodilation this way
Name four corticosteroids used in the treatment of asthma
- Beclomethasone
- Budesonide
- Fluticasone
- Mometasone
_ and _ are two biologics that work against IL-5 to treat asthma
Mepolizumab and Reslizumab are two biologics that work against IL-5 to treat asthma
_ is a biologic that blocks the IL-5 receptor
Benralizumab is a biologic that blocks the IL-5 receptor
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Corticosteroids are used in the treatment of asthma because they _ and _
Corticosteroids are used in the treatment of asthma because they promote anti-inflammatory mediators and inhibit inflammatory mediators
Corticosteroids bind hormones and cause changes in _
Corticosteroids bind hormones and cause changes in transcription and translation
* Increase transcription of anti-inflammatory mRNA
* Decrease transcription of inflammatory mediators
Corticosteroids (inhibit/ upregulate) NF-kappaB
Corticosteroids inhibit NF-kappaB
* NFkB mediates the induction of various pro-inflammatory genes
Inflammation or tissue injury triggers _ enzyme to convert phospholipids in the cell membrane into arachidonic acid
Inflammation or tissue injury triggers phospholipase A2 enzyme to convert phospholipids in the cell membrane into arachidonic acid
Arachidonic acid can then be converted by _ into leukotrienes or converted by cyclooxygenases into _
Arachidonic acid can then be converted by lipoxygenase into leukotrienes or converted by cyclooxygenases into prostaglandins
Corticosteroids can inhibit the production of arachidonic acid by upregulating the production of _
Corticosteroids can inhibit the production of arachidonic acid by upregulating the production of annexin 1
* Annexin 1 blocks phospholipase A2
Montelukast and zafirlukast work via _
Montelukast and zafirlukast work via binding to the leukotriene receptor
Montelukast and zafirlukast have a target that is located on _ cells
Montelukast and zafirlukast have a target that is located on bronchial smooth muscle cells
Zilueton has a target found in _ cells
Zilueton’s target is found in mast cells and eosinophils
What is the progression of asthma medications for increasing severity?
- SABA
- Add daily corticosteroid
- Daily CS/ LABA
- Add LAMA
- Add oral corticosteroid
Dilation of the distal airspaces with septal destruction describes _
Dilation of the distal airspaces with septal destruction describes emphysema
Hereditary emphysema is caused by a gene mutation that causes A1AT to misfold and remain stuck in the _
Hereditary emphysema is caused by a gene mutation that causes A1AT to misfold and remain stuck in the hepatocyte ER
Explain how smoking, even in the absense of A1AT def can lead to emphysema
Smoking causes damage to the resident epithelial cells that normally release A1AT and also causes recruitment of neutrophils and macrophages which are responsible for secreting elastase
This pattern of emphysema is most likely associated with _
This pattern of emphysema is most likely associated with smoking; this is centrilobular emphysema
This is a gross view of a lung with _
This is a gross view of a lung with centrilobular emphysema
An increase in the _ diameter is common in COPD; this is sometimes called a _ chest
An increase in the AP diameter is common in COPD; this is sometimes called a barrel chest
The most important “treatment” for COPD patients is _
The most important “treatment” for COPD patients is smoking cessation
Our oxygen saturation goal for COPD patients is _
Our oxygen saturation goal for COPD patients is 88-92%
What are the possible complications that this patient may experience?
This patient has bronchiectasis- a pathologic dilation of the airways that leads to impaired mucus clearance, obstructive lung disease, and cough, dyspnea, sputum
Complications include:
* Infection
* Hemoptysis
* Cor pulmonale
* Hypercapnia/hypoxemia
Hemoptysis is usually a sign that the _ arteries are being affected
Hemoptysis is usually a sign that the bronchial arteries are being affected
Sarcoidosis
Sarcoidosis is associated with _ electrolyte abnormality
Sarcoidosis is associated with hypercalcemia
* Granulomas produce calcitrol –> stimulates bone release of calcium
Sarcoidosis is a multiorgan inflammatory disease that is associated with _
Sarcoidosis is a multiorgan inflammatory disease that is associated with thick, well-formed non-necrotizing granulomas
Sarcoidosis granulomas have a focal accumulation of _
Sarcoidosis granulomas have a focal accumulation of epithelioid histiocytes (lymphocytes)
* Recall that these are non-caseating granulomas
* TB, fungi have amorphorous pink debris in the center (necrotizing)
Identify the giant cells, macrophages, and T cells
Sarcoidosis
Pneumoconiosis is caused by an (organic/ inorganic) cause while hypersensitivity pneumonia is caused by an (organic/inorganic) cause
Pneumoconiosis is caused by an inorganic cause while hypersensitivity pneumonia is caused by an organic cause
Explain the pathogenesis of hypersensitivity pneumonia
Inhaled antigen derived from plant/animal protein or microorganism –> lymphocytic inflammation (T cells) –> activation of macrophages –> granulomatous inflammation
Hypersensitivity pneumonia can be diagnosed via the presence of _ antibodies or _ cells on bronchoalveolar lavage
Hypersensitivity pneumonia can be diagnosed via the presence of IgG antibodies against specific antigens or lymphocytosis on bronchoalveolar lavage
Treatment of hypersensitivity pneumonia includes _ and _
Treatment of hypersensitivity pneumonia includes avoidance and steroids
Hypersensitivity pneumonitis histology is characterized by _ and _
Hypersensitivity pneumonitis histology is characterized by pathy peri-bronchiolar and interstitial inflammation and loosely formed granulomas
Subpleural fibrosis and pleural plaques are associated with _
Subpleural fibrosis and pleural plaques are associated with asbestosis
_ is not fibrogenic, but rather inert; it just settles and sits in the lungs
Coal is not fibrogenic, but rather inert; it just settles and sits in the lungs
Idiopathic pulmonary fibrosis is a fibrosis of the _ of unknown etiology
Idiopathic pulmonary fibrosis is a fibrosis of the lung parenchyma of unknown etiology
Usual interstitial pneumonia (UIP) is _
Usual interstitial pneumonia (UIP) is a pattern of histologic findings that often is synonymous with IPF
* Shows honeycombing on CT scan
* We see a dilation of the parenchyma surrounded by fibrosis
In usual interstitial pneumonia we may see fibroblastic or fibrotic foci with temporal heterogeneity which means _
In usual interstitial pneumonia we may see fibroblastic or fibrotic foci with temporal heterogeneity which means various timepoints of fibrosis
* Some young fibrosis (fibroblastic foci)
* Some mature fibrosis (fibrotic foci)
mean pulmonary artery pressure equation
mPAP = LAP + (CO x PVR)
Compared to the systemic arterial vasculature, the pulmonary arterial vasculature is _ pressure and _ resistance
Compared to the systemic arterial vasculature, the pulmonary arterial vasculature is lower pressure and lower resistance
* This is important for the right ventricle which can’t handle high pressures
WHO group 1 of PH includes _
WHO group 1 of PH includes PAH
WHO group 2 of PH includes
WHO group 2 of PH includes left heart disease
WHO group 3 of PH includes
WHO group 3 of PH includes lung disease
* Hypoxic vasoconstriction
* Sleep apnea
* Destruction of blood vessels (emphysema, fibrosis)
WHO group 4 of PH includes
WHO group 4 of PH includes chronic thromboembolism
“Plexiform lesion” is associated with _
“Plexiform lesion” is associated with pulmonary arterial hypertension (Group 1)
* Narrowing of the arterial lumen –> increased PVR
Pulmonary arterial hypertension is often idiopathic; heritable PAH is often caused by a mutation of the _ gene
Pulmonary arterial hypertension is often idiopathic; heritable PAH is often caused by a mutation of the BMPR2 gene
Secondary causes of PAH
Secondary causes of PAH
* Schistosomiasis
* HIV
* Scleroderma and other connective tissue diseases
* Drug/ toxins
Pulmonary hypertension patients will often present with _ symptoms
Pulmonary hypertension patients will often present with exertional dyspnea, lightheadedness, fatigue, peripheral edema, weight gain, sometimes angina and syncope
Exam findings of PH might include:
Loud P2, TR murmur, parasternal heave & sometimes signs of RV failure
Right heart catheterization is necessary for PAH diagnosis to determine that mPAP > _
Right heart catheterization is necessary for PAH diagnosis to determine that mPAP > 20 mm Hg
