Flashcards in Respiratory Review/ interstitial disease (6)- Melissa** Deck (89):
How many lobes are in the right and left lung respectively?
Describe why aspirated objects are more likely to lodge in the right lower lobe than in the left lung.
Right lung = 3 lobes
Left Lung - 2 lobes
Left has Less Lobes!!!
*Right main stem bronchus is vertical--easier route for aspirated objects*
Describe the progression of the bronchial tree; where are cartilage and submucosal glands found?
Trachea--> Bronchi--> Bronchioles (*No cartilage or submucosal glands)--> Terminal Bronchioles--> Acinus (respiratory bronchioles+ alveolar ducts + alveolar sacs)
How many terminal bronchioles constitute a pulmonary lobule?
3-5 terminal bronchioles
What structures constitute an acinus? (3)
What is another name for this structure?
*Terminal respiratory unit*
1. respiratory bronchioles
2. alveolar ducts
3. alveolar sacs
What type of epithelium lines (most of) the respiratory tree?
What area in the tree is NOT lined by this type of epithelium?
What type of epithelium lines this area?
- pseudo stratified, ciliated, tall (simple) columnar epithelium lines most of the resp tree
- vocal cords are lined by simple squamous epithelium
Where do we find mucus secreting goblet cells and glands in the respiratory tree?
What disease state causes excessive formation of goblet cells?
Cartilaginous airways (Trachea and bronchi) have goblet cells and glands
*ASTHMA causes excessive formation of goblet cells and glands--may cause tumor like clusters. If you see cilia on biopsy assume benign.
What are the two cell types that make up the alveolar epithelium? Which one constitutes most of the epithelium? What roles does each cell play?
Type I pneumocytes: 95% of alveolar surface
Type II pneumocytes: 5% alveolar surface; produce surfactant and participate in repair
Describe the arterial supply to the lung:
Pulmonary AA's: form heart
Bronchial AA's: from aorta
List three pulm defense mechanisms:
1. Nasal clearance (sneeze, cough, blow nose)
2. Trachiobroncheal clearance (epithelial mucocilliary action)
3. Alveolar Clearance (phagocytosis by alveolar MQs)
How do ETOH and smoking compromise our resp. defense mechanisms? (2)
1. ETOH + smoking both interface with MQ phagocytosis
2. Smoking destroys mucocilliary apparatus
What are two important examples of how pulmonary congestion and edema can compromise pulm. defense?
- Bronchial obstruction
Describe examples of conditions in which patients are predisposed to lung infection: (3)
1. Viral infection predisposes to bacterial infection
2. All other forms of immunosuppression including splenic insufficiency
3. **Also: He doesn't say it but FOR SURE CF cause the bugs live in all of the extra slime.
Define restrictive lung disease.
How does the disease influence the following:
4. FEV1 : FVC Ratio
Restrictive lung disease refers to REDUCED EXPANSION of lung parenchyma--caused by either diseased lung tissue itself or chest wall probs.
1. TLC: decreases
2. FEV1: decreases (MAY stay same)
3. FVC: decreases THE MOST
4. FEV1: FVC ratio INCREASES/ is normal
What are 4 chest wall disorders that can cause restrictive lung disease?
4. pleural disease
What exactly IS interstitial lung disease?
How does it effect lung capacity and DLCO?
How common is it?
1. Inflammation or fibrosis of lung CT/ alveolar septal interstitium-->
2. DECREASED lung capacity, compliance, and volume
3. INCREASED diffusion barrier = DECREASED DLCO
~15% non infectious pulm disease
(So far less common than COPD spectrum)
What are the components of the interstitium?
Includes basically everything EXCEPT vessels and pneumocytes!
1. BM of endothelial and epithelial cells
5. mast cells, lymphs, monocytes
Restrictive disease: symptoms
What is heard on auscultation and observed on PE?
What is seen on CXR?
What is the ultimate sequelae of these diseases? (2)
***FINE DRY CRACKLES AND CLUBBING!!!!***
--CXR: diffuse infiltrate
Cor Pulmonale + *Honeycomb Lung*
Describe the primary pathogenesis mechanism
associated with Idiopathic Pulmonary Fibrosis/ Usual Interstitial Pneumonia (IPF)/(UIP)
Telomerase dysfxn --> excess apoptosis --> Constant Inflammation/repair (TNFa) --> FIBROBLASTIC FOCI in lung
What is a fibroblastic focus and what causes its formation?
With what is it assc?
Proliferation caused by constant inflammation and healing (mediated by TNFa)
*Asstd with IPF/UIP
Describe the gross morphology of IPF/UIP--which area of the lungs does this disease primary affect?
"cobblestone" pleural surface
Describe the microscopic morphology of IPF/UIP; how does it change from early to late disease? (2)
Fibroblastic foci--> honeycombing
*lesions will demonstrate TEMPORAL HETEROGENEITY and MILD/MODERATE INFLAMMATION*
What is honeycomb lung and with which diseases is it associated (2)?
- Honeycomb lung refers to dense fibrosis + cystic spaces lined by TYPE II pneunocytes
- Associated with IPF/UIP, severe asbestosis
What is meant by temporal heterogeneity?
With which disease is it associated?
Abrupt transition from healthy to diseased tissue in the fibrotic lung--associated with IPF/UIP
What are the 5 dead giveaways Sigdel gave in class that should ALWAYS point to IPF/UIP?
1. fibroblastic foci
2. dense fibrosis
4. temporal heterogeneity
5. mild/ moderate inflammation
Age of onset
Tx/Prog: ONLY TRANSPLANT; mean survival= 3 years
Nonspecific Interstitial Pneumonia (NIP):
How is this disease defined?
What are its two morphologies? Better prognosis?
Lacks histo features of other interstitial diseases
1. cellular (better prognosis)
Describe the CELLULAR morphology of NIP:
uniform mild/moderate interstitial inflammation (better prognosis)
- no fibrobastic foci, honeycomb, temporal heterogeneity
Describe the FIBROSING morphology of NIP:
Diffuse/ patchy fibrosis
WITHOUT temporal heterogeneity, no fibroblastic foci, no honeycomb
Age of onset
Sx: cough + dyspnea for mos
Tx/ prog: steroids; good prognosis
Cryptogenic Organizing Pneumonia (COP):
Describe the pathogenesis
Response to ANY sort of infection/ inflammation; most commonly infections.
Describe the morphology of COP
*MASSON BODIES* in bronchioles and alveoli
=polypoid plugs of loose fibrous CT
(All lesions are same age)
CXR: peribronchial consolidation (may involve Hilar nodes)
Tx/ prog: steroids for 6+mos; spontaneous resolution
What is Pneumoconiosis?
What are three examples of this type of disease?
Diffuse interstitial disease from chronic inhalation of particles
1. Coal workers pneumoconiosis
3. asbestos related disease
What are the 4 factors influencing the outcome of ALL pneumoconiosis?
1. amount of toxin inhaled
2. size of particle (small are worse! 1-5um)
3. solubility/ physiochemical properties
4. smoking = damage to mucociliary apparatus
What are two reasons why smaller particles are more dangerous or cause pneumoconiosis?
1. lodge deeper in air smaller terminal airways
2. can reach toxic levels
What are the three degrees of Coal Workers Pneumoconiosis; who can get this disease (3)?
1. Asymptomatic Anthracosis
2. Simple CWP
3. Complicated CWP (progressive massive fibrosis)
*Can affect smokers, miners, urban dwellers*
Describe the morphology of asymptomatic anthracosis: (3)
- carbon particles & pigmented MQs in pulm lymphatics
- NO CELLULAR RXN
--Which part of the lung is affected?
--What might this disease cause?
Carbon laden MQs form macules --> nodules (w. Collagen)
- Affects resp bronchioles of UPPER LOBES
- May cause emphysema
Describe the morphology of COMPLEX CWP:
What do the lesions contain?
What is the end stage of this disease called?
Three buzz words?
- 2+ cm Black lesions w/ NECROTIC centers
- Lesions contain COLLAGEN and CARBON
- PROGRESSIVE MASSIVE FIBROSIS (PMF) = end stage
necrosis, collagen, carbon
Describe the typical clinical course for CWP; which populations are at risk (3)?
- Typically benign & does not usually progress to PMF
Population: smokers, miners, urban dwellers
What is Caplan Syndrome?
What are the hallmarks of the disease? (2)
-Pneumoconiosis + RA
- RAPID GROWING LUNG NODULES (may mistake for tumor)
- (Central necrosis w/ surrounding fibroblast, MQ, collagen matrix)
What are the two morphologies of silicon dioxide particles? How do they induce disease?
1. Crystalline (BAD)
2. Amorphous (typically quartz; not as severe)
Silica inhaled--> Activate MQs--> release mediators--> fibrosis ensues decades after exposure
What are 4 of the mediators released by MQs in response to silica?
4. Fibrogenic cytokines
Describe the morphology of SILICOSIS (2):
Where in the lungs does it manifest?
*UPPER LUNG ZONES*
1.SCARS: concentric hyalinized collagen inside dense capsule
2.EGG SHELL calcifications*: (fibrosis of hilar nodes + pleura)
4 C's: concentric collagen in capsules and calcifications
What are two diseases that this condition predisposes patients to get?
#1 OCCUPATIONAL DISEASE WORLD WIDE
- CXR: nodules in upper lung zones
- *Predisposed to TB and malignancy*
List 4 potential sequelae of asbestos:
Which is most common?
#1: FIBROUS PLEURAL PLAQUES
2. pleural effusion
3. interstitial fibosisis
4. malignancy: extrapulm tumors, ***bronchogenic carcinoma>>> mesothelioma***
What are the two types of Asbestos fibers?
How do they cause disease?
Which one is worse?
Soluble curly fibers--> bronchocillary removal
2. AMPHIBOLE FIBERS
*MORE PATHOGENIC; LESS COMMON*
Stiff, brittle fibers--> lodge in deep lung tissue
What are the two ways in which asbestos can be carcinogenic?
1. carcinogens bind asbestos
2. activates MQs to release ROS--> TOOMAH!
Describe how asbestos fibers cause fibrosis
Where in the lung does this happen (early vs. late disease)?
Cause MQs release chemotactic/ fibrogenic mediators
EARLY: Acini (respi bronchioles etc)
LATER: Diffuse Interstitial Fibrosis (like IPF/UIP), HONEYCOMBING, extends to pleura
What are asbestos bodies?
What do they look like?
- Asbestos fibers with proteins +/- Fe
- Golden brown, fusiform/ beaded dumbbell looking rods with translucent center
*Ferruginous bodies* contain Fe
What is the most common manifestation of asbestosis in the lungs? What are they made up of (2)? Do these structures contain asbestos bodies?
- Dense collagen, Ca++
- DO NOT CONTAIN ASBESTOS BODIES
Asbestos Related Disease:
Onset is how long after exposure?
CXR: where do you see densities?
Onset: 20 years after exposure
CXR:densities in LOWER LOBES
List three causes of therapy induced restrictive lung disease and the mechanism by which they cause disease:
Bleomycin: direct damage to lung tissue
Amiodarone + radiation: pneumonitis (pulm fibrosis)
What are the two granulomatous restrictive lung diseases?
2. hypersensitivity pneumonitis
Refresh your memory: what is a granuloma?
Infectious or noninfectious organized collection of MQs (epithelioid cells/ histiocytes)
How is sarcoidosis diagnosed?
List 4 immunological dysfunctions associated with the disease?
What genetic mutations are associated with this disease?
Dx of exclusion; bronchoscopes give ^ diagnostic yield
1. ^ CD4+ T cells
2. ^ IL2, IL8
3. ^ IFN-g, TNF
4. ^ MQ inflammatory protein
Genetic mutations: HLA-A1, HLA-B8
Describe the microscopic morphology of sarcoidosis:
What FOUR things do the sarcoid granulomas include?
**Noncaseating granulomas--> fibrous scars**
The granulomas include:
1. Tight epithelioid cells
2. Langhan (giant) cells
3. Schaumann bodies (Ca/protein)
4. Asteroid bodies (sellate inclusions inside giant cells)
How does sarcoidosis manifest in the lung/ mediastinum?
- "bilateral hilar lympadenopathy"
- granulomas in resp. lymphatics, bronchi, vasculature
(all of the tubes-- carrying blood lymph or gas!)
How does sarcoid manifest in liver and spleen? (2)
- splenic involvement without enlargement
- liver granulomas in portal tracts
Does sarcoid affect bone marrow; if so where?
- granulomas in marrow of hands and feet
Describe how sarcoid can affect skin and eyes:
skin: nodules/ plaques/ lesions (it varies)
eyes: iritis, dacroadenitis
What is Mikulicz Syndrome? (4)
Sarcoidosis effecting GLANDS (First 3 must be bilateral):
(bilateral salivary glands involved + lacrimal)
Patient population that gets sarcoidosis (2)?
Tx/Prognosis--who has the best prognosis?
Population: AA women (10X); southeastern US
Sx: mimic lung cancer
CXR: "bilateral hilar lymphadenopathy"
Prog: Best if hilar/ pulm involvement only, not systemic
Why is early dx critical?
Hypersensitivity to INHALED Ags: type III or IV
***NOT assc with ^^^ eos.
*Can cause interstitial fibrosis if not diagnosed or treated early!*
Three examples of hypersensitivity pneumonitis + their associated Ag:
1. Farmer's lung: thermophilic actinomyocytes
2. Pigion Breeder's lung: proteins from feathers or poops
3. Humidifier Lung: thermophilic bacteria from heated H2O
How does early hypersensitivity pneumonitis look on histo?
What if it is left untreated?
LOOSE NONCASEATING granumomas --> honeycombing if not treated
Describe how acute hypersensitivity pneumonitis presents:
What about late stage/ untreated?
- 4-6 hours after re-exposure to Ag see fever, dyspnea, cough + nodular infiltrate on CXR
- cyanosis; decreased lung capacity (restrictive disease)
Describe ACUTE Eosinophilic Pneumonia:
What causes the disease?
How is it diagnosed?
Hypersensitivity to INHALED antigens
- Dx: BAL (lavage) 25%+ EOS
-Clinical: RAPID fever/dyspnea/hypoxemia--> Resp Failure
- TX: Steroids
Describe SIMPLE pulmonary eosinophilia/ Loffler's Syndrome:
Hypersensitivity to FOOD or DRUG (#1 Sulfadrug)
- ^^ eos in BLOOD
- lung lesions with eos and giant cells @ septae
Tx/Prog: Benign/ self limiting
Describe SECONDARY Pulmonary Eosinophilia:
Common clinical comorbidities/ associations (2)?
Hypersensitivity to INFECTION (parasitic, bacterial, fungal)
C: commonly associated with asthma, aspergillosis allergy
Prog: can lead to CHRONIC lung injury and FIBROSIS
Three parasites known to cause secondary pulm eosinophilia?
Chronic Eosinophilic Pneumonia:
Related to AUTOIMMUNE disease
- peripheral lung consolidation
- lymphs + EOS infiltrate septae + alveoli
Tx: responds well to steroids
What is pulmonary alveolar proteinosis (PAP)?
What are the three subtypes?
Which is most common?
Protein material accumulates in lung (^ lung size/weight)
Describe the pathogenesis
90% of all cases
GM-CSF Auto Abs--> DECREASE MQ fxn--> SURFACTANT + Proteins accumulate in alveolar space
What is the prognosis?
*FATAL WITHOUT LUNG TRANSPLANT (Death 3-6mos)*
- Rare cause of NRDS
- Associated with various gene mutations
With what is this disease associated? (3)
Associated with silicosis, malignancy, immunodeficiency
Describe the morphology of all PAP subtypes: (2)
-PAS + precipitate and consolidation
- (+/-) cholesterol clefts
Who gets PAP?
Clinical presentation/ CXR?
CP: PRODUCTIVE GELLY COUGH!!!
CXR: scattered consolidation
Tx: Use BAL to give GM-CSF therapy
Prog: can cause respiratory failure; esp in congenital type
What are the two interstitial lung diseases associated with smoking?
1. Desquamative interstitial pneumonitis
2. Respiratory Bronchiolitis
(really the same disease with RB being worsened DIP)
Desquamative Interstitial Pneumonitis
vs Respiratory Bronchiolitis Assc Interstitial Disease: how do they differ in terms of morphology?
DIP: pigment laden MQs in alveoli only
RB-ILD: pigment laden MQs in alveoli, bronchioles and peribronchiolar areas + Fibrosis
Desquamative Interstitial Pneumonitis (DIP) + Respiratory Bronchiolitis Assc Interstitial Disease (RB-ILD) :
Middle aged male smokers
TX: steroids + smoking cessation
Triad that should make you think respiratory bronchiolitis?
2. Liver fibrosis
3. Pigmented MQs
#1 respiratory disease worldwide
Two restrictive diseases that present in the LOWER lobes? Two in the UPPER lobes?
-Upper: Silicosis, Coal Workers
-Think of lower as MORE SEVERE!
(asbestos, IPF-- the same two that cause honeycomb)
Condition assc with "temporal heterogeneity"
Three hypersensitivity related pneumonitis conditions:
1. "hypersensitivity" pneumonitis
(type III, IV --> granulomas)
2. Acute eosinophilic pneumonitis
3. Simple pulmonary eosinophilia
(ingested antigens --> go to GI first and spread to lungs)
What are the four eosinophilic pnuemonitis conditions?
What are their very broad causes
-acute (inhaled allergen)
-simple (ingested antigen)
-chronic (AI disease)
Of the four eosinophilic pneumonitis conditions, which can lead to a chronic/ fibrotic disease?
(simple, chronic are self limiting)