Lecture 16: ILD Flashcards
1
Q
what are the Interstitial lung diseases?
A
- -A heterogeneous group of lung disorders marked by inflammatory changes in the alveoli. ILDs can be idiopathic or due to secondary causes such as autoimmune disease, or exposure to drugs or toxic substances.
- -Multitude of diseases that cause FIBROSIS of the pulmonary parenchyma/interstitium, resulting in restrictive defect on pulmonary function.
2
Q
examples of ILDs?
A
- -Pneumoconiosis
1) Inhaled organic and inorganic dust
2) Hypersensitivity pneumonitis - -Fibrosis associated with connective tissue disorders
1) SLE, rheumatoid arthritis, scleroderma, dermatomyositis - -Sarcoidosis
- -Idiopathic pulmonary fibrosis (i.e unknown etiology)
- -Drugs (eg Bleomycin, Radiation, etc)
3
Q
ILDs cause obstructive or restrictive patterns?
A
restrictive
4
Q
what is the interstitial space?
A
The interstitial space is defined as loose connective tissue throughout the lung (alveolar walls and septae)
5
Q
what are the 3 subdivisions of the interstitial space of lung?
A
1) Bronchovascular: the area surrounding the bronchi, arteries, and veins from the root of the lung to the respiratory bronchiole
2) Parenchymal: situated between the alveolar and capillary basement membranes
3) Subpleural: situated beneath the pleura, as well as the interlobular septae
6
Q
how ILD is diagnosed?
A
Interstitial lung disease is diagnosed by a combination of radiographic features in combination with clinical signs and symptoms, but can be diagnostically and therapeutically challenging!!
7
Q
does interstitial space is visible radiographically?
A
The interstitium of the lung is not normally visible radiographically; it only becomes visible when it involved in a disease process, which increases its volume and attenuation.
8
Q
what is the hallmark of ILDs?
A
Hallmark of this disease is FIBROSIS or SCARRING
9
Q
what is the result of fibrosis and scarring in the lungs?
A
As the alveolar walls become fibrotic and scarred, diffusion of oxygen and carbon dioxide is impaired, resulting in lack of oxygen transfer to blood, causing hypoxaemia and dyspnoea.
10
Q
what is the most common ILD?
A
- -Idiopathic pulmonary fibrosis (IPF): most common
- -Risk factors: cigarette smoking, environmental or occupational exposures, chronic aspiration, genetic predisposition
11
Q
what are the occupational, environmental, and iatrogenic causes of ILD?
A
1) Pneumoconioses
- -Asbestosis
- -Silicosis
- -Rare pneumoconioses (e.g., berylliosis, anthracosis)
2) Radiation pneumonitis
12
Q
what medications can cause lung fibrosis?
A
–Chemotherapeutic agents: bleomycin , methotrexate, busulfan
Other agents: amiodarone , nitrofurantoin, phenytoin, –penicillamine, cocaine, and heroin
13
Q
what are the bleomycin and busulfan?
A
1) A metal-chelating, glycopeptide antibiotic that has a cytotoxic effect on nondividing tumor cells by causing fragmentation of DNA chains. Used to treat lymphomas, germ cell tumors, head and neck cancers, and squamous cell carcinoma. Adverse effects include fever, hypersensitivity reactions, skin changes, and severe pulmonary fibrosis.
2) An alkylating chemotherapeutic agent of the alkyl sulfonate class. Often used in bone marrow ablation prior to transplantation for chronic lymphocytic leukemia. Common adverse effects include severe myelosuppression, electrolyte imbalance, hyperpigmentation, cardiac, pulmonary, and hepatic toxicity.
14
Q
what are the ILDs secondary to underlying disease?
A
1) Granulomatous ILD:
- -Sarcoidosis: noncaseating granulomas in multiple organs, including the lung
- -Pulmonary Langerhans cell histiocytosis
- -Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
- -Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
2) Infectious diseases (eg, tuberculosis, legionellosis)
3) Alveolar filling disease
4) Hypersensitivity reactions ( hypersensitivity pneumonitis and eosinophilic pneumonitis)
5) Connective tissue disorders
6) Bronchoalveolar carcinoma
15
Q
the alveolar filling disease includes…
A
Includes Goodpasture’s syndrome, idiopathic pulmonary hemosiderosis, and pulmonary alveolar proteinosis (rare condition caused by accumulation of surfactant-like protein and phospholipids in alveoli)
16
Q
what CTDs can cause ILDs?
A
rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and mixed connective tissue disease
17
Q
how ILDs are classified?
A
1) Etiology
2) Radiology
- -Based on zones of fibrosis
- -Upper, mid, lower, widespread
3) Histology
18
Q
what are the ILDs that predominantly involve upper lung zones?
A
- -Sarcoidosis
- -Langerhans cell Histiocytosis
- -Coal workers pneumoconiosis
- -Ankylosing spondylitis
- -Radiation
- -Silicosis
19
Q
what are the ILDs that predominantly involve lung mid zones?
A
- -TB
- -Chronic EAA
20
Q
what are the ILDs that predominantly involve lung lower zones?
A
- -Rheumatoid arthritis
- -Asbestosis
- -IPF
- -Drugs
- -Scleroderma
- -Collagen vascular disease
21
Q
what are the pneumoconioses?
A
A group of restrictive interstitial lung diseases caused by the inhalation of certain dust, often affecting miners and agricultural workers. Asbestosis and silicosis are the most common types.
22
Q
inorganic vs organic pneumoconioses?
A
1) Inorganic (mineral dust pneumoconioses)
- -Asbestosis, silicosis, coal, Beryllium
2) Organic
- -Extrinsic allergic alveolitis/hypersensitivity pneumonitis
- -Mouldy hay, bird feces, cotton fibers
23
Q
In ILD, large particles (>10 mcm) are deposited in terminal bronchioles, alveolar ducts, and alveoli and result in fibrosis and granuloma formation. T/F
A
False Small particles (<10mcm)
24
Q
what are the factors of particles that influence pathogenicity?
A
- -Size
- -Shape
- -Chemical composition
- -Concentration
- -Solubility
- -Particle reactivity
- -Duration of exposure
- -Co-existence of other lung diseases
Particles1-5um may reach alveoli – most dangerous size
Particles >5-10um are unlikely to reach distal alveoli
<0.5um tend to act like gases and move into and out of alveoli without causing damage
Shape - > Long and thin eg asbestos
25
how particle size and shape influence ILD pathogenicity?
- -Particles1-5um may reach alveoli – most dangerous size
- -Particles >5-10um are unlikely to reach distal alveoli
- -<0.5um tend to act like gases and move into and out of alveoli without causing damage
- -Shape - > Long and thin eg asbestos
26
5-10 mcm size particles are the most dangerous. T/F
False
| particles 1-5um may reach alveoli – most dangerous size
27
what is the coal worker's pneumoconiosis?
A severe form of anthracosis that occurs with prolonged exposure to coal and carbon dust. Characterized by nodular opacities (typically <1 cm) in the upper lobes of the lung and chronic bronchitis that can progress to pulmonary fibrosis.
- -Anthracosis: heterogeneous pulmonary infiltrates, with/without mass lesion
- -Coal workers' pneumoconiosis: fine nodular opacifications (< 1 cm) in upper lung zone
28
who is at risk for acquiring coal workers pneumoconiosis?
- -City dwellers
| - -Coal miners
29
what are the characteristic features of coal worker's pneumoconiosis?
1) Milder than other types of pneumoconiosis
2) Pulmonary fibrosis rarely occurs.
3) Coal workers' pneumoconiosis (also known as black lung disease or black lung):
- -A more severe form of anthracosis
- -Occurs only with prolonged exposure to large amounts of coal
- -Carbon-laden macrophages induce inflammation
- -Characterized by chronic bronchitis that progresses to progressive massive pulmonary fibrosis
30
coal worker's pneumoconiosis affects upper or lower lung zones?
upper
31
what is the silicosis?
Silicosis is a common occupational lung disease that is caused by the inhalation of crystalline silica dust.
32
who is at increased risk for silicosis?
- -Workers that are involved for example in construction, mining, or glass production are among the individuals with the highest risk of developing the condition.
- -Sand blasting, quarrying, mining, stone cutting, foundry work, ceramics
33
what occupational group is at risk of acquiring asbestosis?
Mining, milling, fabrication of ores and materials, installation and removal of insulation
34
what occupational group is at risk of acquiring berylliosis?
Nuclear energy and aircraft industries
35
what causes lung injury inpneumoconioses
Inhalation of inorganic dust – especially chronic, occupational exposure – causes an inflammatory reaction in the lung parenchyma
- -FIBROGENIC FACTORS (TNF, PDGF)
- -PROINFLAMMATORY FACTORS (LTB4, IL-8, IL-6)
- -TOXIC FACTORS (proteases, ROS)
36
what is the spectrum of disease of coal worker's pneumoconiosis?
1)Pulmonary anthracosis
--Most innocuous coal induced pulmonary lesion
--Commonly seen in urban dwellers and smokers
Inhaled carbon pigments taken up by alveolar macrophages, accumulate in connective tissue along lymphatics and in lymph nodes
2)Simple coal workers' pneumoconiosis (CWP)
3)Complicated CWP
4)Caplan syndrome
37
what is Caplan syndrome?
Caplan syndrome (pneumoconiosis in combination with rheumatoid arthritis) → rapid development of basilar nodules and mild obstruction of ventilation
38
what are the features of simple coal workers' pneumoconiosis (CWP)?
- -Focal dust accumulation around respiratory bronchioles
- -Characterised by coal macules and larger coal nodules
- -Macules consist of dust-laden macrophages
- -Nodules are a collection of collagen fibers
- -Upper zone predominant
- -Can eventually cause dilatation of alveoli leading to centrilobular emphysema
- -Usually not functionally disabling
39
what are the microscopic lesions of coal workers pneumoconiosis?
Microscopically the lesions consist of dense collagen and pigment, often with central necrosis due to ischemia
40
what are the features of complicated coal worker's pneumoconiosis?
- -Also called Progressive Massive Fibrosis (PMF)
- -Develops after 10-20 years
- -Occurs on a background of simple CWP by coalescence of the coal nodules
- -Intensely black scars; usually multiply
- -Microscopically the lesions consist of dense collagen and pigment, often with central necrosis due to ischemia
- -Upper zone predominant
- -Massive confluent fibrosis
- -Minority of cases lead to increasing pulmonary dysfunction, pulmonary hypertension, and cor pulmonale
- -Progression of CWP to PMF linked to coal dust exposure level and total dust burden
41
progression of CWP to PMF depends on...
coal dust exposure level and total dust burden
42
what are the complications of CWP?
Minority of cases lead to increasing pulmonary dysfunction, pulmonary hypertension, and cor pulmonale
43
Caplan syndrome occurs with what pneumoconioses?
- -This syndrome also occurs in asbestosis and silicosis
- -Definition: Co-existence of rheumatoid arthritis with pneumoconiosis leading to the development of distinctive nodular pulmonary lesions that develop fairly rapidly
- -Nodules exhibit central necrosis surrounded by palisading fibroblasts, plasma cells, macrophages containing coal dust and collagen
44
nodules in Caplan syndrome are composed of...
Nodules exhibit central necrosis surrounded by pallisading fibroblasts, plasma cells, macrophages containing coal dust and collagen
45
amorphous silica is the most dangerous. T/F
False
Silica occurs in crystalline and amorphous forms, but crystalline forms (quartz, cristobalite, tridymite) are more toxic and fibrogenic
46
what occupations are at risk for acquiring silicosis?
- -Rock cutting
- -Mining
- -Drilling
- -Tunnelling
- -Stonemasons
- -Sandblasters
- -Glass and pottery making
47
what are the forms of silicosis?
1) Acute silicosis
- -Exposure to very high levels of silica; develops quickly after exposure
- -Rapid onset tachypnoea, cough, cyanosis and respiratory failure
- -Histology: Interstitial inflammation and accumulation of proteinaceous fluid in alveolar spaces
2) Chronic (nodular) silicosis
- -Inhalation over a prolonged period of time
- -Formation of characteristic fibrotic silicotic nodules
- -Upper zone and subpleural predominant
3) Complicated (conglomerate) silicosis
- -Progression of chronic silicosis
- -Expansion and coalescence of nodules, destruction of lung parenchyma (PMF)
4) Other pulmonary disease associations
- -Increased risk of TB
- -Caplan syndrome
- -Lung carcinoma
- -Clinical course:- Progressive respiratory failure, pulmonary hypertension and cor pulmonale
48
what is the pathophysiology of silicosis?
- -Inhalation of silica dust → deposition in the airways → interaction of crystalline silica surfaces with aqueous media produces oxygen radicals → inflammatory reaction and injury to pulmonary cells (e.g., alveolar macrophages) ) → pulmonary fibrosis and scarring
- -The smaller the particles, the further down they infiltrate the airways. Particles ≤ 1 μm in diameter are more likely to be deposited in the smaller sections of the lower airways, e.g., the respiratory bronchioli.
- -Macrophages also actively phagocytize the silica particles, which causes an inflammatory reaction in itself.
49
Does silicosis involve upper or lower lung zones?
upper
50
what are the clinical features of chronic silicosis?
- -Chronic silicosis refers to long-term exposure to crystalline silica dust. Patients may remain completely asymptomatic or develop symptoms only after several decades of exposure
- -Chronic cough (often with sputum) and exertional dyspnea
- -Fatigue and weight loss
- -Signs of respiratory failure and cor pulmonale
- -Special form: Caplan syndrome (pneumoconiosis in combination with rheumatoid arthritis) → rapid evelopment of basilar nodules and mild obstruction of ventilation
51
what is the asbestosis?
- -A type of lung disease caused by the inhalation of asbestos fibers, usually as a result of occupational exposure.
- -Asbestos is a family of crystalline hydrated silicates
52
what are the sources of asbestos?
- -Occupations involving the manufacture or demolition of ships, plumbing, roofing, insulation, heat-resistant clothing, and brake lining
- -individuals with moderate, persistent exposure are also at risk (e.g., persons responsible for washing contaminated workwear, electricians, or painters who work close to insulation sites). Asbestos is a highly resilient material that is optimal for insulation and was extensively used before its dangers were known.
- -Smoking: Smoking is associated with a higher rate of disease progression and has a synergistic effect with asbestos, further increasing the risk of lung cancer.
53
what are the types of asbestos?
- -Serpentine (curly, flexible fiber)
- -Amphibole (straight, still and brittle fiber; and are more pathogenic)
1) Chrysotile (serpentine fiber; most used in industry) 2)Amosite
3) Crocidolite
54
what is asbestos?
Asbestos is a naturally occurring silicate. These silicate fibers are either curved (serpentine asbestos such as chrysotile; most common type in the US) or straight (amphibole asbestosis). Fibers with a diameter of < 3 μm are able to penetrate cell membranes. Long fibers (length > 5 μm) settle in the lungs and cannot be successfully phagocytosed. Both are fibrogenic.
55
what is the most common form of asbestos?
serpentine asbestos such as chrysotile; most common type in the US
56
what is the spectrum of disease of asbestos exposure?
1. Pleural plaques, commonest
- -Well circumscribed plaques of dense collagen, most frequently on parietal pleura
2. Pleural effusions
3. Asbestosis
- -Interstitial fibrosis of lungs
- -Lower zone predominant
4. Mesothelioma (pleural and peritoneal)
5. Bronchogenic carcinoma
- -Concomitant smoking greatly increases risk
57
what are the features of asbestosis?
- -The fibres are inhaled, are surrounded in macrophages and coated in iron, producing a dumbbell shaped fibre
- -The iron coating has also resulted in the fibres being called “ferruginous bodies”
- -Latency period of 10-30 years
- -Asbestosis: diffuse pulmonary interstitial fibrosis with asbestos bodies.
- -Begins as fibrosis around respiratory bronchioles and alveolar ducts and extends to involve adjacent alveolar sacs and alveoli.
- -Results in enlarged air spaces enclosed with thick fibrous walls -> honeycombing
- -Begins in lower lobes and subpleurally, but spread upwards to involve middle and upper lobes as the fibrosis progresses.
58
how long is the latency period of asbestosis?
Most patients are asymptomatic for ∼ 15–20 years after exposure (since the development of disease is dose-dependent).
59
Does asbestosis usually involve lower or upper lung zones?
lower
60
what are ferruginous bodies?
dumbbell-shaped and golden-brown fusiform rods, surrounded by an iron protein coat
61
what stain is used to detect ferruginous bodies?
prussian blue
62
what are the characteristic findings of asbestosis on CXR?
- - diffuse bilateral infiltrates predominantly in the lower lobes
- -Interstitial fibrosis (A hazy appearance of the parenchyma, which may advance to honeycombing in later stages)
- -Supradiaphragmatic and pleural reticulonodular opacities/plaques (nitially, mostly linear infiltrates are seen. Eventually, calcified or non-calcified plaques appear.)
- -Rounded atelectasis (Caused by pleural adhesions)
- -In some cases, pleural effusion
63
what is the significance of pleural plaques in asbestosis?
Pleural involvement is characteristic of asbestos exposure and helps distinguish asbestosis from other interstitial lung diseases.
64
what is the most common malignant complication of asbestosis?
Bronchogenic carcinoma (not mesothelioma !!!!!!)
65
what is the hypersensitivity pneumonitis?
--Inhaled organic antigens cause a type III hypersensitivity immune reaction
--Circulating antibodies react with antigen with precipitation in lung of antigen/antibody complex.
--Acute, but may progress to chronic disease (Type IV hypersensitivity –> pulmonary fibrosis in upper zones)
Farmers lung, Pigeon fanciers lung etc
--An acute, subacute, or chronic pulmonary disease characterized by an immune-mediated inflammatory response in the alveoli and small airways as a result of exposure to a variety of inhaled antigens.
66
what types of HSR involve hypersensitivity pneumonitis?
An acute, subacute, or chronic pulmonary disease characterized by an immune-mediated inflammatory response in the alveoli and small airways as a result of exposure to a variety of inhaled antigens.
67
examples of hypersensitivity pneumonitis
1) avian proteins---Pigeon breeder's lung
2) Actinomycete spores from air conditioners, humidifiers, and water reservoirs--Humidifier lung (air-conditioner setting)
3) Actinomycete spores from moldy hay--Farmer's lung
4) Actinomycete spores from sugar cane--Bagassosis
5) Actinomycete spores from moldy compost--Mushroom worker's lung (compost treatment)
6) Aspergillus clavatus spores from moldy paints--Malt worker's lung
7) Grain weevil dust--Grain handler's lung
8) Various bacteria in saw dust (through logging)--Woodworker's lung
9) Isocyanates (used in the adhesive and foam industry)--Chemical worker's lung
68
what are the clinical features of hypersensitivity pneumonitis?
--Acute febrile episodes
--Headache, malaise, cough dyspnoea
--Bibasal crepitations
--Symptom onset 6-8 hours after antigen exposure
eg moldy hay with thermophilic actinomyces, aspergillus, avian antigens, etc
--Acute setting: symptoms last 24 hours
--May progress to chronic disease via type IV hypersensitivity reaction, causing pulmonary fibrosis (upper zone)
69
what are the features of chronic hypersensitivity pneumonitis?
- -Insidious onset of fatigue, productive cough, progressive dyspnea, cyanosis
- -Bilateral rales
- -Weight loss
- -A recurrent 'common cold' with an irritating cough and fever may indicate hypersensitivity pneumonitis!
70
what is the pathology of HSP?
- -Alveolar walls infiltrated by lymphocytes, plasma cells, macrophages, granulomas
- -Chronic phase is associated with fibrosis - clinical findings often subtle
71
how HSPis diagnosed?
1) Primarily a clinical diagnosis based on history of exposure and typical clinical presentation, which is supported by the presence of any one of the following:
2) Positive serology: IgG, IgA, or IgM antibodies
3) Chest x-ray or CT
- -Acute: Patchy reticulonodular or diffuse infiltrates may be found in the mid to upper zone.
- -Chronic : ground-glass attenuation with honeycombing (fibrotic changes) +/- emphysema
4) Pulmonary function test : restrictive pattern
5) Bronchoalveolar lavage (BAL) : lymphocytic predominance (ighly sensitive method: A normal BAL Virtually excludes hypersensitivity pneumonitis, although lymphocytic predominance may occur in other forms of interstitial lung disease (eg, silicosis).)
72
how HSP is treated?
- -Antigen avoidance (voidance is the most effective form of treatment and is always recommended. If complete avoidance is not possible, then protective devices and proper storage of potential sources of antigens to minimize exposure are recommended.)
- -Glucocorticoid therapy (ay be used as symptomatic therapy for acute or chronic cases. A longer course of treatment is required for chronic cases.)
73
what is the sarcoidosis?
- -Restrictive lung disease
- -Multisystemic disease of unknown etiology characterized by non-caseating granulomata in many tissues.
- -Many diseases (including TB and berylliosis) cause granulomatous inflammation, thus sarcoidosis is a diagnosis of exclusion, requiring the correct clinical and radiological context
- -Always requires clinicopathological correlation (CPC)
- -Involves lungs in 90-95% of cases
74
granulomas in sarcoidosis are caseating or non-caseating?
non-caseating
75
at what ages sarcoidosis is commonly present?
- -Bimodal distribution: 25–35 years old with a second peak for females 45–65 years old
- -Sex: ♀ > ♂ (2:1)
76
what ethnic group is at a higher risk of sarcoidosis?
--Prevalence: 10 times higher among African Americans than whites in the US. African Americans are also more likely to have chronic and more severe disease courses.
77
what is the cause of sarcoidosis?
- -The cause of sarcoidosis is still unknown. Current hypotheses suggest that the etiology is multifactorial.
1) Genetic (ndividuals may have a genetic or HLA-associated predisposition (HLA-DQB1) to developing the disease.)
2) Environmental agent exposure
3) Infectious agents
78
what is the pathophysiology of sarcoidosis?
1) T-cell dysfunction and increased B-cell activity result in local immune hyperactivity and inflammation.
2) Formation of non-caseating granulomas within the lungs and the lymphatic system
- -Macrophages activate Th1 cells.
- -Th1 cells stimulate the formation of epithelioid cells and multinucleated giant cells by releasing IFN-γ.
- -Epithelioid cells produce an angiotensin-converting enzyme (ACE) and release cytokines, which recruit more immune cells.
- -A mature granuloma is composed of epithelioid cells and macrophages in the center, which are surrounded by lymphocytes and fibroblasts.
3) Fibrosis and subsequent damage of organs and tissue: Epithelioid cells secrete cytokines to recruit fibroblasts, which cause fibrosis.
4) Calcium dysregulation: activated macrophages produce 1-α hydroxylase → ↑ 1,25 hydroxyvitamin D (hypervitaminosis D) → hyperphosphatemia, hypercalcemia, and possibly renal failure
79
what cells are accumulated in sarcoidosis in the lungs?
There is an accumulation of CD4 T lymphocytes accompanied by release of IL-2
80
do smokers are at increased risk for sarcoidosis?
No
- -11/100,000 in whites
- -36/100,000 African Americans
- -Female > Male (2:1)
- -Age of onset: 25-40 years
- -High incidence in Sweden and Denmark and also among US African Americans
- -Higher prevalence in non smokers
81
what organs can be involved in sarcoidosis?
1) Lungs: 90-95% of patients
- -Bihilar adenopathy
- -Interstitial inflammation progressing to diffuse interstitial fibrosis -> pulmonary hypertension -> cor pulmonale
2) Skin: 25% patients
- -Erythema nodosum
- -Lupus pernio
3) Eyes: 20-50%
- -Iritis
- -Iridocyclitis
- -Retinitis
- -Optic nerve involvement
4) Parotid gland: 10%
- -Painful enlargement
5) Spleen: 10%
6) Liver
7) Heart
8) Brain
9) Bone marrow: 40%
10) Kidneys, musculoskeletal, cranial nerves
82
what are the features of acute sarcoidosis?
- -Typically has a sudden onset and remits spontaneously within approx. 2 years
- -Progression to chronic sarcoidosis is rare.
- -General: fever, malaise, lack of appetite, weight loss
- -Pulmonary: dyspnea, cough, chest pain
- -Extrapulmonary: arthritis, anterior uveitis, erythema nodosum
83
what is the lupus pernio?
pathognomonic, extensive, purple skin lesions (violaceous skin plaques) on the nose, cheeks, chin, and/or ears; also referred to as epithelioid granulomas of the dermis
84
which nerve palsy is common in sarcoidosis?
cranial nerve palsy (7th cranial nerve palsy is the most common)
85
what are the cardiac manifestations in sarcoidosis?
Often asymptomatic, but restrictive cardiomyopathy, pericardial effusion, AV block, dysrhythmia, or even sudden cardiac death may occur
86
CRUELING in sarcoidosis?
Features of sarcoidosis are GRUELING: Granulomas, aRthritis, Uveitis, Erythema nodosum, Lymphadenopathy, Interstitial fibrosis, Negative TB test, and Gammaglobulinemia.
87
what is the most frequent extrapulmonary manifestation in sarcoidosis?
Peripheral lymph nodes are the most frequent site of extrapulmonary manifestation (40%).
88
what is Lofgren syndrome?
- -Highly acute clinical presentation of sarcoidosis with fever and the following triad of symptoms
- -Migratory polyarthritis: symmetrical arthritis that primarily affects the ankles
- -Erythema nodosum: primarily affects the extensor surface of the lower legs
- -Bilateral hilar lymphadenopathy
89
what are the clinical features of sarcoidosis?
- -Asymptomatic/incidental finding
- -Eg screening CXR
- -30% present with respiratory symptoms
1) SOB, dry cough
2) Other non-specific: fever, fatigue, weight loss, night sweats, anorexia
- -Peripheral lymphadenopathy
- -Cutaneous lesions
- -Eye involvement
- -Neurosarcoidosis
- -Lofgren's syndrome: fever, erythema nodosum, polyarthritis (often ankles) and bilateral hilar lymphadenopathy
- -Mikulicz's syndrome: combined uveoparotid involvement
90
what is Mikulicz syndrome?
A condition characterized by enlargement of the parotid, salivary, and/or lacrimal glands. Can sometimes involve the tonsils. Can cause dry mouth and dry eyes. Associated with several underlying disorders, including leukemia, lymphoma, systemic lupus erythematosus, and Sjögren syndrome.
91
what investigations should be performed in suspected sarcoidosis?
1) CXR
2) CT thorax
3) PFT’s (restrictive defect)
4) ECG
5) Bloods:
- -Calcium often raised
- -Alkaline phosphatase
- -Serum ACE
- -Renal / liver / bone profile
6) A sampling of nodes: the most common site is hilar nodes
7) Procedure: EBUS-TBNA (endobronchial ultrasound, transbronchial needle aspiration)
8) Must send the sample to microbiology for C&S, to exclude infectious aetiologies of granulomatous inflammation
92
what diseases should be excluded in suspected sarcoidosis?
- -Other causes of granulomatous inflammation
- -Infection (TB), foreign body, hypersensitivity pneumonitis, silicosis, berylliosis, vasculitic disorders involving the lung, malignancies (eg lymphoma/carcinomas can show adjacent granulomatous inflammation)
93
does the clinical course of sarcoidosis is predictable?
- -Unpredictable course
- -May remain asymptomatic
- -Progressive chronicity
- -Periods of activity interspersed with periods of remission
- -Respiratory involvement may progress to diffuse interstitial fibrosis (10-15%), and lead to pulmonary hypertension and cor pulmonal
- -Visual impairment
- -Usually steroid responsive
94
what is the treatment of sarcoidosis?
1) Isolated pulmonary sarcoidosis: In most cases, no treatment is required. The disease is often asymptomatic, non‑progressive, and has a high rate of spontaneous remission.
2) Symptomatic or extrapulmonary sarcoidosis
- -First line: glucocorticoids
- -Second line: alternative immunosuppressive therapy (e.g., methotrexate or azathioprine), possibly in combination with glucocorticoids
- -Antimalarial drugs (e.g., chloroquine, hydroxychloroquine): Found to be useful in cutaneous or neurological lesions, and in hypercalcemia
- -Last resort in severe pulmonary disease: lung transplantation
- -NSAIDs are always indicated for symptom relief.
95
what is the idiopathic pulmonary fibrosis?
--Pulmonary disorder of unknown aetiology characterised histologically by diffuse interstitial fibrosis
The most common interstitial lung disease. --Characterized by irreversible pulmonary fibrosis and impaired pulmonary function. The conditions takes an insidious course that initially presents with exertional dyspnea that progresses to dyspnea at rest, persistent nonproductive cough, and fatigue. Progression to respiratory failure usually occurs within 3–7 years.
96
IPF is more common in males or females?
- -M>F
| - -2/3rds >60 years
97
what is the pathogenesis of IPF?
- -Alveolar wall injury -> interstitial oedema and accumulation of inflammatory cells (alveolitis)
- -If the injury is persistent, cellular interactions involving lymphocytes, macrophages, neutrophils and alveolar epithelial cells, leading to proliferation of fibroblasts and progressive interstitial fibrosis
98
what cytokines are involved in the pathogenesis of IPF?
Activated alveolar epithelial cells release potent fibrogenic cytokines and growth factors. These include, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), platelet-derived growth factor, insulin-like growth factor-1, and endothelin-1 (ET-1). These cytokines and growth factors are involved in the migration and proliferation of fibroblasts and the transformation of fibroblasts into myofibroblasts. Fibroblasts and myofibroblasts are key effector cells in fibrogenesis, and myofibroblasts secrete extracellular matrix proteins.
99
what are the pathologic features of IPF?
--The inflammatory response that heals by fibrosis
--Early stage: Interstitial inflammation / pneumonitis
IPF is histologically called usual interstitial pneumonia
--The hallmark for UIP is the heterogeneous appearance of areas of fibrosis and inflammation alternating with areas of normal lung. The inflammation is usually patchy
--Advanced stage: lung spaces are separated by inflammatory fibrous tissue giving “honeycomb change”.
100
what is the pathologic hallmark of IPF?
The hallmark is the heterogeneous appearance of areas of fibrosis and inflammation alternating with areas of normal lung. The inflammation is usually patchy
101
what are the radiological features of IPF?
- -Bilateral interstitial shadowing
- -Patchy or nodular
- CT: Honeycombing and traction bronchiectasis
- -Reticular opacities
- -Subpleural, lower zone predominant in IPF
102
IPF commonly involves upper or lower lung zones?
Subpleural, lower zone predominant in IPF
103
what are the clinical features of IPF?
- -IPF usually presents insidiously with gradual onset of dry cough and progressive dyspnoea
- -Clubbing
- -Age: >60 years
- -Physical examination: Characteristic “velcro crackles” on inspiration
- -As the disease progresses, leads to cyanosis, cor pulmonale (loud P2, parasternal heave, raised JVP) and peripheral edema
104
at what age IPF usually presents?
>60 years
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what investigations should be performed in suspected IPF?
- -Radiology: CXR, HRCT Thorax
- -PFT’s (restrictive defect)
- -Blood tests (FBC, U&E, LFT’s, Calcium ABG)
- -Exclude other causes eg connective tissue diseases
- -ECG, Echocardiogram (functional assessment)
- -+/- Bronchoscopy
- -+/- Biopsy (VATS – video-assisted thorascopic surgery; only performed if the presentation is atypical)
106
what is the ARDS?
- -Syndrome of reduced pulmonary gas exchange caused by diffuse injury to the alveolar-capillary barrier.
- -The alveolus is filled with proteinaceous fluid and there is a marked infiltrate of acute inflammatory cells
- -Form of noncardiogenic pulmonary edema resulting from acute damage to the alveoli
- -Most patients with the syndrome will die without supplemental oxygen and assisted ventilation
- -Common condition affects both medical and surgical patients
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what are the common causes of ARDS?
1) DIRECT LUNG INJURY
- -Pneumonia
- -Aspiration of gastric contents
2) INDIRECT LUNG INJURY
- -Sepsis
- -Severe trauma with shock and multiple
- -transfusions
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what is the pathophysiology of ARDS?
--Epithelial barrier is composed of Type 1 cells which are flat and make up 90% of the alveolar surface and are easily injured, and Type 2 cells which are cuboidal and are more resistant to injury
- -Neutrophils accumulate in early stages
- -Cytokines are released
- -Macrophages also release cytokines
109
what cells are initially accumulated in ARDS?
neutrophils
110
the epithelial barrier of alveoli is composed of...
Epithelial barrier is composed of Type 1 cells which are flat and make up 90% of the alveolar surface and are easily injured
111
how ARDS is diagnosed?
- -IN AT RISK PATIENT RAPID ONSET OF RESPIRATORY FAILURE
- -Arterial hypoxemia difficult to treat
- -CXR: Bilateral pulmonary infiltrates
- -Similar to cardiogenic pulmonary edema
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what is the characteristic feature of ARDS on CXR?
Bilateral pulmonary infiltrates
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what is the prognosis of ARDS?
- -Ventilation may contribute to lung injury: alveolar overdistension with repeated collapse and reopening may stimulate inflammatory cytokine release
- In the acute phase, sloughing of bronchial and alveolar epithelial cells with formation of protein-rich hyaline membranes on the denuded basement membrane
- -If uncomplicated, rapid resolution occurs
- -Others progress to fibrotic lung injury
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what is the characteristic histopathological finding in ARDS?
protein-rich hyaline membranes
