Respiratory Pathology Flashcards
1
Q
what is atelectasis
A
refers to an area of airless pulmonary parenchyma due to collapse or incomplete expansion
2
Q
what is resorption atelectasis
A
- complete obstruction of an airway
- air within the dependent lung is resorbed -> collapse
- mediastinum shifts toward the affected lung
3
Q
what is compression atelectasis
A
- fluid, tumor, or air accumulate within the pleural space, preventing normal expansion
- mediastinum shifts away from the affected lung
4
Q
what is contraction atelectasis
A
- pulmonary or pleural fibrosis preventing normal expansion
- not reversible
5
Q
what is hemodynamic pulmonary edema
A
- intra alveolar fluid accumulation due to increased hydrostatic pressure in the pulmonary circulation
- hemosiderin-laden macrophages may be seen within alveoli with chronic pulmonary edema
- decreased oxygenation, increased chance of infection
6
Q
what is edema secondary to microvascular (alveolar) injury
A
- injury to and inflammation of alveolar vascular endothelium and/or respiratory epithelium
- infectious or toxic insults
- may be localized or diffuse
7
Q
what is obstructive lung disease chracterized by
A
an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles
8
Q
what will pulmonary function tests show in obstructive lung diseases
A
decreased maximal flow rates during forced expiration
9
Q
what are the diseases in obstructive lung diseases
A
- emphysema
- chronic bronchitis
- asthma
- bronchiesctasis
10
Q
which groups are more susceptible to COPD
A
women and african americans
11
Q
what is the association of COPD and smoking
A
- strong
- approximately 35-50% of heavy smokers develop COPD
- 80% of COPD is due to smoking
12
Q
what is emphysema
A
destruction of airway walls and irreversible enlargement of the airways distal to the terminal bronchiole
13
Q
what are the classifications of emphysema
A
- centriacinar
- panacinar
- distal acinar
- irregular
14
Q
describe centriacinar emphysema
A
- occurs predominantly in heavy smokers, often along with chronic bronchitis (COPD)
- the respiratory bronchioles are involved, sparing the distal alveoli
- more lesions are seen in the upper lobes/ apical segments
15
Q
describe panacinar emphysema
A
- associated with alpha1 antitrypsin deficiency
- alveoli distal to the respiratory bronchioles are involved
- occurs more frequently in the lower and anterior aspects of the lungs - lung bases are most severely involved
16
Q
what is the pathogenesis of emphysema
A
- exposure to injurious particles in tobacco smoke stimulates inflammation
- imbalance of proteases and antiproteases
- oxidative stress
17
Q
how does exposure to injurious particles in tobacco smoke stimulate inflammation
A
- lung epithelial cells and macrophages release chemotactic factors to recruit inflammatory cells from circulation
18
Q
what releass destructive proteases
A
inflammatory cells
19
Q
what causes oxidative stress
A
smoke, inflammatory cell products containing oxidants, continuing the cycle of tissue damage and inflammation
20
Q
what is alpha-1 antitrypsin deficiency
A
- alpha 1 antitrypsin is a potent antiprotease, encoded by the Pi locus on chromosome 14
- homozygotes for the Z allele (0.012% of US population) have a significant decrease in alpha 1 antitrypsin
- 80% of homozygotes will develop symptomatic panacinar emphysema, accelerated and more severe if the patient smokes
21
Q
how is emphysema an obstructive lung disease
A
- small airways are normally held open by the elastic recoil of lung parenchyma
- destruction of elastic alveolar walls surrounding respiratory bronchioles leads to the collapse of those bronchioles during expiration
22
Q
describe the clinical course of emphysema
A
- no symptoms until one third of lung tissue is affected
- initial symptoms include dyspnea, cough and wheezing
- with severe emphysema: weight loss, barrel chest, prolonged expiration
23
Q
what might emphysema progress to
A
pulmonary hypertension and right sided heart failure
24
Q
what is death from emphysema usually due to
A
- respiratory failure
- RHF
- pneumothorax -> lung collapse
25
what is chronic bronchitis and what population is common
- a chronic, persistent productive cough without any other identifiable cause
- common in smokers and inhabitatns of polluted environments
26
what is the pathogenesis of chronic bronchitis
- initiating factor is exposure of the bronchi to inhaled irritants
- mucus hypersecretion
- chronic inflammation -> damage and fibrosis of small airways
- diminished ciliary action of respiratory epithelium, leading to stasis of mucus
27
what are the morphologic changes with chronic bronchitis
- edema and swelling of the respiratory mucosa, often with squamous metaplasia
- hyperplasia of submucosal mucous glands of the trachea and larger bronchi (thickness of the mucus gland layer increases)
- increased goblet cells in small bronchi and bronchioles and extensive small airway mucous plugging
28
what is the clinical course of chronic bronchitis
- persistent productive cough
- dypsnea on exertion
- classically: hypercapnia, hypoxia, mild cyanosis
29
what is asthma
- chronic disorder of the conducting airways characterized by:
- recurrent bronchoconstriction associated with a variety of stimuli
- inflammation of bronchial walls
- increased mucus secretion
30
what are the symptoms of asthma
- recurent wheezing, shortness of breath/chest tightness, cough
- more frequently at night/early morning
31
describe atopic asthma
- type I (IgE mediated) hypersensitivity reaction
- usually onset in childhood
- triggered by a variety of allergens: dust, animal dander, dust, foods
- patients may have high serum IgE, a positive skin test for the inciting allergen or may demonstrate IgE antibodies to specific allergens and often have a family history of asthma
32
what is atopic asthma pathogenesis
- sensitization occurs when Th2 cell in response to antigen presentation stimulate producion of IgE (IL4, IL13) recruits eospinophils (IL5) and stimulates mucus production (IL13)
- IgE binds to Fc receptors on mast cells
33
describe the reaction upon re exposure to antigen in atopic asthma pathogenesis
cross linking of IgE molecules on mast cells, triggering degranulation and inducing the immediate hypersensitivity reaction
34
the immediate phase of atopic asthma pathogenesis is characterized by:
- bronchoconstriction
- mucus secretion
- increased vascular permeability
35
the late phase (hours) of atopic asthma is characterized by
- recruitment of more inflammatory cells ( neutrophils, eosinophils, lymphocytes)
- results in damage to the mucosal tissue
36
in non atopic asthma bronchoconstriction is triggered by:
- respiratory viruses
- inhalation of irritants
- cold air
- exercise
37
what are the morphologic changes in asthma
- repeated allergen exposure and reaction induced airway remodeling which includes:
- bronchial wall smooth muscle hypertrophy and hyperplasia
- subepithelial fibrosis
- submucosal gland hyperplasia; increased goblet cells
- increased airway vascularity
- increased thickness of the airway wall
38
what are the morphologic changes in severe cases of asthma
bronchi and bronchioles become occluded by thick mucus plugs, which may be expelled in sputum or BAL specimens (Curschmann spirals)
- sputum and BAL specimens may also contain numerous eosinophils and charcot- leyden crystals
39
what is the clinical course of asthma
- attacks may last hours, but some patients may experience symptoms at a lower baseline level constantly
- in severe acute asthma the attack may last for days and result in obstruction sufficient to cause death
40
what is bronchiectasis
- chronic recurrent necrotizing infections eventually destroy smooth muscle and elastic tissue, leadig to permanent dilation of bronchi and bronchioles
- the infection with associated inflammation and destruction may follow obstruction and impedance of normal drainage; of severe bronchial infections may cause enough inflammatory damage and necrosis to bring about the bronchiectatic changes
41
what are the predisposing conditions for bronchiectasis
- conditions affecting mucus clearing (primary ciliary dyskinesia, cystic fibrosis, other bronchial obstruction)
- immunodeficiency conditions
42
repeated attempts to resolve the inflammatory process in bronchiectasis may result in______
peribronchial fibrosis
43
what are pneumoconioses
- nontumor lung diseases in the setting of exposure to mineral dusts, inorganic and organic particles and chemical fumes
44
what is particle pathogenicity influenced by
- particle size (1-5um are most pathogenic)
- particle solubility
- level and duration of exposure. effectiveness of clearance
- intensity of immune response
45
what is coal workers lung disease
- simple coal workers pneumoconiosis
- inhaled carbon dust is taken up by macrophages which accumulate in interstitial tissue along pulmonary lymphatic tissue
46
what is anthracosis and what population is it seen in
- black pigmented lesions formed by these coal dust containing macrophages
- can also be seen in smokers and in urban dwellers
- can occasionally cause centriacinar emphysema
47
what is complicated coal workers pneumoconiosis characterized by
multiple anthracotic scars, which if extensive may lead to:
- respiratory failure
- pulmonary hypertension and RHF
48
what is silicosis
- caused by inhalaing crystalline silicon dioxide over long periods of time
- most common occupational disease worldwide
- crystalline particles are ingested by macrophages which then mount an inflammatory response
- slowly growing nodular collagenous scars
- over time these may coalesce -> progressive massive fibrosis
49
describe silicosis morphology
- the nodular scars may occur in the lungs or in hilar lymph nodes - calcified lymph nodes can sometimes be identified with x-ray
- the nodules are characteristically formed of whorled balls of dense collagen fibers, surrounded by dust containing macrophages
- initially more prominent apically
- the silica particles are birefringent with plane polarized light
50
what is the clinical course of silicosis
- rate of onset and disease progression is extremely variable, progression may occur even after exposure ceases
- silicosis leads to increased susceptibility to TB
- patients with silicosis have twice the risk of lung cancer
51
describe asbestos related pulmonary diseae
- asbestos refers to a group of fibrous hydrated silicate crystals known to cause interstitial and pleural fibrosis and lead to lung carcinoma and malignant mesothelioma
52
what are the two types of asbestos related pulmonary disease
serpentine and amphibole
53
describe asbestos related lung disease
- asbestos fibers are taken up by macrophages which then initiate an inflammatory response leading to interstitial fibrosis
- may result in honeycomb lung
- the lung bases are affected first and it progresses upward
54
what does asbestos related lung disease look like
- plaques of dense collagen, sometimes calcified may form on the pleura, particularly the parietal pleura
- occasionally asbestos exposure may result in pleural effusion
55
clinically, in asbestos related lung disease, patients presents with findings similar to:
pneumoconiosis or usual interstitial pneumonia
56
pleural plaques are usually:
asymptomatic
57
asbestosis complicated by ________carries a poor prognosis
lung or pleural malignancy
58
what is the prevalence of pulmonary infections
very common- causes 1 out of 6 deaths in the US
59
what are the systemic conditions which may predispose to pulmonary infection
- immunodeficiency
- chronic disease
60
what defense mechanisms specific to the lungs will be compromised in pulmonary infections
- cough reflex
- impaired or diminished ciliary function
- mucus stasis
- decreased pulmonary macrophage activity
- pulmonary edema
61
what is community acquired bacterial pneumonia
- infections of bacterial pathogens may be indistinguishable from viral, clinically and radiologically
- bacterial pneumonia may follow a viral URI
62
what are the predisposing conditions for community acquired bacterial pneumonia
- age: young or old
- chronic disease (COPD, diabetes, CHF)
- absent splenic function - predisposes toward encapsulated bacterial infections)
63
what are the causative organisms in community acquired bacterial pneumonia
-streptococcus pneumoniae:
- hemophilus influenzae:
- moraxella catarrhalis
- pseudomonas aureginosa
- legionella pneumophilia
- mycoplasma pneumonia
64
what are the morphologic changes in pulmonary infections and what patterns does consolidation occur in
invasion of bacteria leads to alveolar filling with inflammatory cells and exudate, resulting in consolidation of the lung tissue
- consolidation occurs in two patterns: bronchopneumonia, lobar pneumonia
65
what is bronchopneumonia
- patchy involvement of lung parenchyma
- consolidated areas may coalesce
- formed of acute suppuration
- basal, often multilobar, and frequently bilateral
66
what are the morphologic changes in lobar pneumonia and what are the 4 stages
- consolidation occupies an entire lobe
- occurs in 4 stages:
- congestion: vascular engorgement, cell poor intraalveolar fluid with bacteria
-red hepatization: robust exudate with neutrophils, erythrocytes disintegration, early organization
- resolution: organizing fibrosis admixed with macrophages
67
what is the clinical course of community acquired bacterial pneumonia
-presents with abrupt fever, shaking chills, productive cough
- lobar pneumonia x ray: opaque lobe
- bronchopneumonia x-ray: focal opacities
- antibiotics: culture and sensitivity
- complications include: abscess, empyema, bacteremia
68
what are the common organisms in community acquired viral pneumonia
- influenza viruses A, B, and C, RSV, human metapneumovirus, adenovirus, rhinovirus, coronaviruses
69
what are the predisposing factors to community acquired pneumonia
very young and elderly
- malnutrition/alcoholism
- chronic disease
70
describe COVID 19 transmission and clinical course
- SARS-CoV-2
- transmission through respiratory droplets
- variable clinical course: potential for abnormally increased cytokine response, potential for development of arterial and venous thrombosis
71
Type A influenza virus infects:
humans, swine, birds and horses
72
influenza virus genome is composed of:
8 segmnets
73
why does constant antigenic drift occur with influenza virus
viral RNA polymerase lacks error detection capability
74
how does a pandemic with influenza occur
- recombination of segments of the genome may occur when an individual is coinfected with different types -> antigenic shift leading to a new viral strain -> pandemic
75
what does the influenza virus infect
- upper respiratory tract
- respiratory epithelium
76
lung infection in influenza virus may be:
patchy or extensive
77
extent of influenza disease in host is affected by:
- host immune status
- virulence of the infecting strain
- presence/absence of other complication conditions
78
describe tuberculosis transmission and mechanism and causative organism
- mycobacterium tuberculosis
- transmission via airborne droplets
- entry into macrophages -> replication within macrophages -> bacteremia and seeding of multiple sites
- immune response: cell mediated (3 weeks) -> macrophage activation and development of tissue hypersensitivity
- granulomatous inflammation/tissue damage
79
describe primary tuberculosis
- infection of a previously unexposed and unsensitized patient
- development of a Gohn complex
- results in a focus of pulmonary scarring
- approximately 5% will develop significant disease at this point
80
what is a Gohn complex
a focus in the lung parenchyma with consolidation/necrosis and hilar lymph nodes with caseating necrosis
81
what does progressive primary tuberculosis most commonly occur in
immunocompromised host
82
desscribe secondary tuberculosis
- arises in a previously sensitized host, from dormant primary lesions
- usually multiple lesions involving the apices of one or both lungs
- spread through the blood may result in military TB
- isolated organ TB: from hematogenous seeding- may be the presenting manifestation
83
where is military TB most prominent
liver, bone marrow, spleen, adrenal glands
84
what is Pott disease
involvement of vertebrae in secondary TB
85
what is aspiration pneumonia
occurs in debilitated patient with diminished swallowing reflex
- aspirated gastric content-> abscess
- usually more than one organism, usually anaerobes
86
what is hospital acquired pneumonia and what are the causative agents
- patients typically very ill, often on a ventilator
- often immunocompromised
- enterobacteriaceae, pseudomonas, S. aureus
87
what is a carcinoma
- lung cancer is the most common cause of cancer mortality world wide
- overall 5 year survival rate of 16%
- closely related to smoking
- most cases are between 40-70 with peak incidence in the 50-60s
88
describe how smoking affects lung cancer
- 80% of lung cancer occur in active or recent smokers
- direct relationship between cancer frequency and pack year history
- some people may be genetically susceptible to tobacco smoke: polymorphisms of cytochroms P-450 mono oxygenase
- environmental exposure: asbestos, uranium, vinyl chloride
89
describe squamous cell carcinoma
- strong association with tobacco smoke
- high frequency of p53 mutations and overexpression
- often preceded in bronchial epithelium by squamous metaplasia, dysplasia, and carcinoma in situ
- most often arise in the central lung/hilar region
90
describe adenocarcinoma
- may occur in smokers or non smokers
- more likely to be peripheral
- gain of function mutations involving growth factor receptor pathways: EGFR, ALK, ROS, MET, RET, KRAS
-precursor lesions include: atypical adenomatous hyperplasia (less than or equal to 5mm). adenocarcinomma in situ (less than 3cm). cells are more atypical and may be mucinous
91
describe small cell carcinoma
- strongest association with smoking
- frequent TP53 and RB mutations
- aggressive very high rate of fatality
- may arise centrally or peripherally likely from neuroendocrine cells in the bronchial epithelium
92
what do cells in small cell carcinoma look like
- tumor cells are small with little cytoplasm, closely arranged nuclei with molding and absent nucleoli
- cells grow in clusters without any architectural pattern
- necrosis may be marked
93
describe large cell carcinoma
- poorly differentiated subtype of NSCC without neuroendocrine squamous or glandular differentiation
- diagnosis of exclusion and accounts for approximately 10% of cases
94
describe metastatic lung carcinoma
- any type of lung cancer may spread to the pleural space
- may spread hematogenously or within lymphatics: mediastinal, bronchial, paratracheal nodes
- metastasis may occur widely particularly to: adrenal glands (>50%), liver (30-50%), brain (20%), bone (20%)
95
describe tumors metastatic to the lung
- the lung is the most common site of tumor metastasis
- may receive metastases via blood or lymphatics
- most common growth pattern is multiple scattered nodules
96
what are the common primary sites of tumors metastatic to the lung
breast
- colon
- kidney
- prostate
- urinary bladder
97
describe carcinoid tumors
- part of a spectrum of tumors arising from bronchial neuroendocrine cells: neuroendocrine tumorlets, carcinoid tumors, SCC
- 1-5% of all lung tumors, M=F <40
- low grade malignant neoplasm: typical and atypical
- may be central or peripheral
- organoid nests of regular cells containing moderately abundant cytoplasm and regular round nuclei
-atypical carcinoids show more cell variability and higher mitotis activity
98
which carcinoid tumor is more likely to invade lymphatic vessels
atypical carcinoids
99
central carcinoids often protrude into:
the bronchial lumen
100
what symptoms are associated with carcinoid tumor
-coughing
- hemoptysis
- impaired drainage
101
carcinoid syndrome, caused by tumor cells secreting vasoactive amines resulting in:
- flushing
- diarrhea
- cyanosis
102
what is the 5 year survival rate for typical carcinoids and atypical carcinoids
- typical: 95%
- atypical: 70%
103
what is malignant mesothelioma
- increased incidence with asbestos exposure, compound by smoking
- most common mutational abnormality is homozygous deletion of p16 seen in 80%
- mesothelioma arises from visceral or parietal pleura, spreads in the pleural space, eventually ensheating and compressing the lung
- may invade adjacent thoracic structures
104
what are the types of malignant mesotheliom
epithelioid and sarcomatoid types
105
what is used to differentiated between malignant mesothelioma and adenocarcinoma
IHC
106
what are the symptoms of malignant mesothelioma
- chest pain
- dyspnea
- recurrent pleural effusions
- concurrent asbestos related interstitial fibrosis
107
what is the survival of malignant mesothelioma
- 1 year survival is about 50%
- most do not survive 2 years
108
describe squamous papillomas
- squamous lined fronds with fibrovascular cores
- may be single or multiple, and may occur in children and in adults
- caused by HPV types 6 and 11
- benign but may recur
109
describe laryngeal carcinoma
- squamous cell carcinoma typically in men, 50s, and smokers
- thought to arise from dysplastic squamous epithelium: squamous hyperplasia> dysplasia > carcinoma
- carcinoma often forms a bulky, fungating mass protruding from the laryngeal surface, often with ulceration
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