(15+16) Respiratory pathology Flashcards
1
Q
What do the conducting airways consist of? (lung anatomy)
A
- trachea
- left and right main bronchi
- segmental and smaller bronchi
- bronchioles, terminal bronchioles
2
Q
The respiratory bronchioles terminate in the lung acini where gas exchange occurs. What makes up the acini?
A
- alveolar ducts
- alveolar sacs
- alveoli
3
Q
How many lung acini make up a lobule?
A
3 to 5
4
Q
What is the histology of the conducting airways of the lungs?
A
Pseudostratified ciliated columnar mucus secreting epithelium
5
Q
What is the histology of the alveoli?
A
Mostly flat type I pneumocytes (gas exchange)
Some rounded type II penumocytes (surfactant production)
6
Q
What is the function of the type I pneumocytes in the alveoli?
A
Gas exchange
7
Q
What is the function of the type II pneumocytes in the alveoli?
A
Surfactant production
8
Q
Respiratory failure is defined as having a PaO2 of what?
A
Less than 8.0kPa
9
Q
Respiratory failure is due to defective what?
A
- ventilation
- perfusion
- gas exchange
10
Q
What defines type I respiratory failure?
A
paO2 less than 8.0kPa
paCO2 less than 6.3kPa
Hypoxic respiratory drive
11
Q
What defines type II respiratory failure?
A
paO2 less than 8.0kPa
paCO2 more than 6.3kPa
Hypercapnic respiratory drive
12
Q
What are the general respiratory signs and symptoms?
A
- sputum
- cough
- stridor
- wheeze
- pleuritic pain
- dyspnoea
- cyanosis
- clubbing
- weight loss
13
Q
What is the difference between stridor and wheeze?
A
Stridor = inspiratory sound, proximal airway obstruction
Wheeze = expiratory sound, distal airway obstruction
14
Q
How may sputum be described?
A
- mucoid
- purulent
- haemoptysis
15
Q
What is a cough?
A
Reflex response to irritation
16
Q
What causes pleuritic pain?
A
Pleural irritation
17
Q
What causes dysponea?
A
Impaired alveolar gas exchange
18
Q
What causes cyanosis?
A
Decreased oxygenation of haemoglobin
19
Q
When might you get weight loss?
A
Catabolic state with chronic inflammation or tumours
20
Q
What are you looking for on auscultation of the lungs?
A
- crackles (fine or coarse)
- wheeze
- bronchial breathing
- pleural rub
21
Q
When do you get fine crackles on auscultation of the lungs?
A
Resisted opening of small airways
22
Q
When do you get coarse crackles on auscultation of the lungs?
A
Excessive fluid within the lungs
23
Q
What is/when do you get bronchial breathing?
A
Sound conduction through solid lung
24
Q
When do you get pleural rub on auscultation of the lung?
A
Relative movement of inflamed visceral and parietal pleura
25
What are you listening for on percussion of the lungs?
- dull
| - hyper-resonant
26
What might lungs that are dull on percussion suggest?
Lung consolidation or pleural effusion
27
What might lungs that are hyper-resonant on percussion suggest?
Pneumothorax or emphysema
28
Give some categories of lung diseases
- neoplasms
- infections
- obstructive airways diseases
- interstitial lung diseases
- vascular diseases
- pleural diseases
- occupational lung diseases
- paediatric lung pathology
29
Give some examples of infections affecting the lungs
- pneumonia
| - tuberculosis
30
Give some examples of obstructive airways diseases
- asthma
| - COPD
31
Give some examples of interstitial lung diseases
- adult respiratory distress syndrome
- fibrosing alveolitis
- sarcoidosis
32
Give some examples of vascular lung diseases
- pulmonary embolism
| - pulmonary hypertension
33
Benign primary lung tumours are rare. Give one example
Adenochondroma
34
What percentage of primary lung tumours are malignant carcinomas?
90%
35
What percentage of lung carcinomas are due to smoking?
80%
| secondary cigarette smoke - 10-30% increase
36
How many deaths from malignant primary lung tumours are there in the UK every year?
35,000
| 8% of male deaths, 4% of female deaths
37
What causes 10% of male lung carcinomas?
Asbestos
High level exposure, with or without asbestosis
About 2000 cases per year in UK
38
What 3 main lung diseases does asbestos cause?
- mesothelioma
- lung cancer
- asbestosis
39
What are the risk factors for lung carcinoma?
- smoking
- asbestos
- lung fibrosis
- radon
- chromates, nickel, tar, hematite, arsenic, mustard gas
40
What is squamous metaplasia?
Metaplastic change from pseudostratified columnar epithelium of the bronchus to stratified squamous type which may keratinise (like skin)
- caused by irritants such as smoke
41
What percentage of primary lung tumours are malignant carcinomas?
90%
42
What percentage of lung carcinomas are due to smoking?
80%
| secondary cigarette smoke - 10-30% increase
43
How many deaths from malignant primary lung tumours are there in the UK every year?
35,000
| 8% of male deaths, 4% of female deaths
44
What causes 10% of male lung carcinomas?
Asbestos
High level exposure, with or without asbestosis
About 2000 cases per year in UK
45
What 3 main lung diseases does asbestos cause?
- mesothelioma
- lung cancer
- asbestosis
46
What are the risk factors for lung carcinoma?
- smoking
- asbestos
- lung fibrosis
- radon
- chromates, nickel, tar, hematite, arsenic, mustard gas
47
What is asbestos?
Fibrous metal silicates,
48
What are the different types of asbestos?
Amphiboles
- blue asbestos (crocidolite)
- brown asbestos (amosite)
Serpentines
- white asbestos (chrysotile)
49
Which is the least dangerous type of asbestos?
White asbestos (chrysotile)
Serpentine
50
Which is the most dangerous type of asbestos?
Blue asbestos (crocidolite)
Amphibole
51
What does high level exposure of asbestos produce?
Pulmonary interstitial fibrosis
- asbestosis
52
What allows you to see asbestos bodies?
Light microscopy
- fibres coated with mucopolysaccharide and ferric iron salts
53
High level exposure to asbestos is associated with higher incidence of what?
All types of lung carcinoma
54
What are the hypotheses concerning asbestos?
fibrosis - no increased risk without asbestosis
fibre burden - dose-related, some risk at all exposure level
55
What are the problems concerning asbestos and lung carcinomas?
effects of smoking - multiplicative risk
diagnosing asbestosis
quantification of asbestos exposure
56
Give some epidemiological evidence FOR the connection between asbestos and lung carcinoma
- increased risk in workers exposed to asbestos
| - increased risk in the absence of "small opacities" on CXR in asbestos exposed workers
57
Give some epidemiological evidence AGAINST the connection between asbestos and lung carcinoma
- no increased risk in low level exposed workers
| - no increased risk in Canadian asbestos mining towns inhabitants with no occupational exposure
58
When is lung carcinoma a 'prescribed occupational disease' in the UK?
- lung carcinoma with asbestosis, asbestos related diffuse pleural fibrosis or silicosis
- lung carcinoma without asbestosis but history of over 5 years work in a high exposure occupation
59
Give some examples of asbestos high exposure occupations
- asbestos insulation work
- ship building and repair
- asbestos textile work
- manufacture of gas masks
60
What are the different types of malignant primary lung tumours?
Carcinoma
- non-small cell carcinoma
- small cell carcinoma
Carcinoid tumours
Others (lymphomas, sarcomas, carcinosarcomas)
61
Which is the most common lung carcinoma?
Non-small cell carcinoma = 85%
Small cell carcinoma = 15%
62
What are the different types of non-small cell carcinoma?
- squamous carcinoma (52%)
- adenocarcinoma (13%)
- large cell neuroendocrine carcinoma
- undifferentiated large cell carcinoma
63
All small cell carcinomas are what?
Neuroendocrine
64
What is a key feature of lung carcinomas?
Multiple differentiation is common
| multiple different lines of differentiation, different characteristics, hard to classify
65
What are carcinoid tumours?
Low grade neuroendocrine epithelial tumours
66
The comments tumours in the lung are what?
Secondary tumours - usually from a known primary but may be the presenting feature of a distant primary tumour
67
Secondary lung tumours are typically what?
Multiple bilateral nodules but can be solitary
68
What do you look for to distinguish between a primary and secondary lung tumour?
- history
- morphology (some adenocarcinomas, but not squamous)
- antigen expression (immunocytochemistry is useful but not 100% reliable)
69
What do lung non-mucinous adenocarcinoma and small cell express? (immunocytochemistry)
- cytokeratin positive
| - thyroid transcription factor positive
70
What do colorectal tumours express? (immunocytochemistry)
- cytokeratin 7 negative
| - cytokeratin 20 positive
71
What do upper gastrointestinal tract tumours express? (immunocytochemistry)
- cytokeratin 7 positive
| - cytokeratin 20 positive
72
What do breast tumours express? (immunocytochemistry)
- may be oestrogen receptor positive
73
What do melanomas express?
- S100
- HMB45
- MelanA positive
- cytokeratin negative
74
What are the sites of lung carcinomas?
- mostly central, main or upper lobe bronchus (bronchogenic)
75
Most lung carcinomas are central but which lung carcinomas are more peripheral?
Adenocarcinoma
- scar cancers or cancer with a fibrous (desmoplastic) reaction?
76
Give some features of squamous carcinoma
- desmosomes link cell like epidermis 'epidermoid'
- may or may not have keratinisation
- more central than peripheral
- 90% in smokers
- cough and haemoptysis
77
Which condition may you get in squamous carcinoma due to parathyroid hormone related peptide?
Hypercalcaemia
78
Describe the normal bronchial epithelium
The normal bronchus is lined by pseudostratified columnar epithelium with ciliated and mucus-secreting cells
79
What is squamous metaplasia?
Metaplastic change from pseudostratified columnar epithelium of the bronchus to stratified squamous type which may keratinise (like skin)
80
How does dysplasia initially begin?
One metaplastic cell undergoes irreversible genetic changes (a series of sequential somatic mutations of oncogenes and anti-oncogenes) producing the first neoplastic cell
81
What happens in developing dysplasia (after the first neoplastic cell has been produced)?
The neoplastic cell proliferates more successfully than the metaplastic cells
The neoplastic clone replaces the metaplastic cells producing dysplasia (intraepithelial neoplasia or carcinoma-in-situ)
82
How does a developing dysplasia go on to form squamous carcinoma?
Neoplastic cells breach the basement membrane producing invasive squamous carcinoma
83
How do neoplastic cells form metastases?
Invading neoplastic cells infiltrate the lymphatic and blood vessels to produce metastases in lymph nodes and distant sites
84
A carcinoma obstructing a bronchus may cause what?
Distal retention pneumonitis
85
Give the key features of adenocarcinoma
A malignant tumour formed from glandular structures in epithelial tissue
Forms in mucus-secreting glands throughout the body
- serous +/- mucus vacuoles
- in acinar, tubular, solid or papillary structures
- 80% in smokers
86
What is expressed in many non-mucinous lung adenocarcinomas?
Thyroid transcription factor (TTF)
87
What is adenocarcinoma in situ also called?
Bronchioloalveolar carcinoma - it is non-invasive
88
What is adeoncarcinoma in situ/bronchioloalveolar carcinoma?
Term describing certain variants of lung cancer arising in the distal bronchioles or alveoli that initially exhibit a specific non-invasive growth pattern. BAC is a type of non-small-cell lung cancer (NSCLC)
Spread of well differentiated mutinous or non-mucinous neoplastic cells on alveolar walls
89
What disease may bronchioloalveolar carcinoma mimic?
Pneumonia
90
What are the neuroendocrine cell proteins identified by immunocytochemistry?
- neural cell adhesion molecule (CD56)
| - neurosecretory granule proteins (chromogranin, snaptophysin)
91
How else can neurosecretory granules be identified?
Electron microscopy (not done in routine clinical practice)
92
What are Kulchitsky cells?
Type of neuroendocrine cell occurring in the epithelia lining the respiratory tract (neuroendocrine cell in normal mucosa)
93
Describe the spectrum of
| malignancy of neuroendocrine tumours
- large cell neuroendocrine carcinoma
- small cell carcinoma
- carcinoid
- atypical carcinoid
94
What do neuroendocrine tumours develop from?
Intraepithelial neuroendocrine cell hyperplasia and carcinoid tumourlets (
95
Give some features of carcinoid tumours
- often grow into and occlude a bronchus
- organoid
- bland cells
- no necrosis
- low mitotic rate
96
What are typical carcinoid tumours associated with?
Multiple endocrine neoplasia syndrom type 1
97
Which type of lung cancer is not associated with smoking?
Typical carcinoid tumours
98
Are carcinoid tumours benign or malignant?
Often thought of as being benign but they are not; they have low malignant potential
May invade lymphatic vessels and nodes but rare distant metastases
6-9% to hilar nodes, less to distant sites
99
What is the general prognosis for typical carcinoid tumours?
95% 5 year survival
100
What percentage of lung carcinoids are atypical?
11%
101
Describe the features of atypical carcinoid tumours compared to typical carcinoid tumours
- less organoid
- more atypia
- nucleoli - may be focal atypia in an otherwise typical carcinoid
- necrosis
- slightly higher mitotic rate (2-10 mitotic figures per 2sqmm compared to
102
What is the prognosis for atypical carcinoid tumours compared to typical carcinoid tumours?
More aggressive than typical carcinoids
- 70% metastasise
- 60% 5 year survival
103
Describe the morphology of large cell neuroendocrine carcinomas
Neuroendocrine morphology
- organoid architecture
- eosinophilic granular cytoplasm
- antigen expression
104
Describe the features of large cell neuroendocrine carcinoma
- severe atypia
- nucleoli
- necrosis
- >11 mitotic figures per 2sqmm
105
What is the prognosis for large cell neuroendocrine carcinomas?
Similar to or worse than other non-small cell lung carcinomas
106
Is large cell neuroendocrine carcinoma associated with smoking?
Yes
107
Describe the main features of small cell carcinoma
- rapidly progressive malignant tumours
- neurosecretory granules with peptide hormones such as ACTH
- may have small primary with metastases before presentation
- 99% in smokers
108
Has there been a "small cell carcinoma in situ" identified?
No
109
Small cell carcinoma usually presents at which stage?
At a late advanced stage with lots of metastases
110
How common are carcinomas with multiple differentiation?
Common
Around 50%, depends on extent of sampling
- mixed NSCLC
- combined small cell carcinoma
111
What is a combined small cell carcinoma?
When a tumour contains a component of small cell carcinoma mixed with NSCLC
112
What is an adenosquamous carcinoma?
Mixed NSCLC
(need 10% of a component for classification)
Contains two types of cells: squamous cells and gland-like cells
113
Describe the features of large cell carcinomas
- no specific squamous or glandular morphology
| - can be neuroendocrine
114
What do 50% of large cell carcinomas express?
Thyroid transcription factor
115
If a large cell carcinoma is neuroendocrine, what will it express?
- CD56
| - neurosecretory granule proteins (synaptophysin, chromogranin)
116
What is lymphangitis carcinomatosa?
Inflammation of the lymph vessels caused by a malignancy
Caused by the dissemination of a tumor with its cells along the lymphatics
117
What are the paraneoplastic effects of lung carcinomas?
- cachexia
- skin - acanthoses nigricans, tylosis
- clubbing
- coagulopathies
- encephalomyelitis, neuropathies and myopathies
- endocrine effects
118
Acanthoses nigricans is a paraneoplastic effect of lung carcinomas. What is it?
Darkened, thickened patches of skin that usually develop in the armpit and around the groin and neck
119
What is the name of the condition that includes clubbing called when related to lung carcinoma?
Hypertrophic pulmonary osteoarthropathy
120
Coagulopathies are a neoplastic effect of lung carcinomas. Give and example
Thrombophebitis migrans
Phlebitis (vein inflammation) related to a thrombus
Thrombophlebitis migrans = occurs repeatedly in different locations
121
What is encephalomyelitis?
Inflammation of the brain and spinal cord, typically due to acute viral infection
122
Which syndrome may you get as a paraneoplastic effect of small cell carcinoma? (neuropathy/myopathy)
Lambert Eaton myasthenic syndrome
- autoimmune disorder
- antibodies against presynaptic voltage-gated calcium channels in the neuromuscular junction
- muscle weakness
123
Give a specific endocrine effect of squamous cell carcinoma
Parathyroid hormone-related peptide caused hypercalcaemia
124
Give a specific endocrine effect of small cell carcinoma
- ACTH
- antidiuretic hormone
from small cell carcinoma
125
Give a specific endocrine effect of carcinoid
- 5-hydroxytryptamine (uncommon)
126
What are the different stages of lung malignancy according to TNM 7th edition?
- T1
- T2
- T3
- T4
127
What are the different factors that are considered in TNM lung malignancy staging?
- diam
- scopy
- atelectasis
- invasion
- nodules
128
What would be the features of a T1 stage lung tumour?
Diam - T1a =
129
What would the features of a T2 stage lung tumour be?
Diam - T2a = 3-5cm, T2b = 5-7cm
Scopy - >2cm to carina
Atelectasis - lobar atelectasis or obstructive pneumonia to hilus
130
What would the features of a stage T3 lung tumour be?
Diam - >7cm
Scopy =
131
What would the features of a stage T4 lung tumours be?
Scopy = tumour in carina
Invasion = Heart, great vessels, trachea, oesophagus, spine
Nodules = nodules in other ipsilateral lobes
132
Give 2 examples of EGFR-TK inhibitors? (Epidermal growth factor receptor tyrosine kinase inhibitors)
- gefitinib (Iressa)
- erlotinib (Tarceva)
They are ATP analogues that inhibit EGFR-TK if activating mutations are present
133
What type of medication is less toxic than standard cytotoxic chemotherapy?
Oral medication
134
What do EGFR-TK inhibitors do?
Inhibition of EGFR-TK mediated protein phosphorylation and activation of the mitotic cycle
135
EGFR-TK sensitising mutations are present in how many cancers and are most common in who?
- 10% of NSCLC
- more common in adenocarcinomas
- more common in non-smoking Asian women
136
Are EGFR-TK inhibitors curative?
Not curative but stabilises progression until resistance mutations develop
137
What does ALK stand for?
Anaplastic lymphoma kinase
138
What happens in ALK gene rearrangements?
inv(2)(p21;p23)
Variable break point inversion on short arm of chromosome 2 fuses ALK and EML genes activating ALK tyrosine kinase
139
An ALK gene rearrangement causes ALK and EML genes to fuse. What does EML stand for?
Echinoderm microtubule like protein
140
How would you detect an ALK gene rearrangement?
Detect mRNA by FISH, CISH of RT-PCR
Low expression so ICC is difficult
141
What cancers are ALK gene rearrangements common in?
Present in about 10% of lung adenocarcinomas
142
Who are ALK gene rearrangements common in?
Non-smoking, Asian women
| independent of EGFR or RAS mutations
143
What does the drug Crizotinib do?
ATP analogue inhibits ALK, ROS1, c-MET (hepatocyte growth factor receptor/HGFR) tyrosine kinases
144
What does use of Crizotinib offer?
Temporary control - no progress or regress
145
How many tumours is Crizotinib effective in?
Effective in about 90% of tumours with ALK-EML fusion gene
FDA approval Aug 2011 for late stage (local advanced or metastatic) NSCLC
UK approval expected
146
What is the condition of air in the pleural cavity?
Pneumothorax
147
What is the condition of transudate or exudate in the pleural cavity?
Pleural effusion (hydrothorax)
148
What is the condition of blood in the pleural cavity?
Haemothorax
149
What is the condition of lymph in the pleural cavity?
Chylothorax (caused by central line in the wrong place, needles through thoracic duct, thoracic duct disrupted by tumour etc)
150
What is the condition of pus in the pleural cavity?
Empyema (pyothorax)
151
What are the inflammatory causes of pleural effusion?
- serous/fibrinous - exudate
| - due to inflammation/infection in adjacent lung
152
What are the non-inflammatory causes of pleural effusion?
Congestive cardiac failure - transudate
153
How can you come up with a diagnosis for pleural effusion?
LDH, pH, glucose of fluid can be measured to suggest a diagnosis
Cytology used to assess the presence of malignant or inflammatory cells
154
What are the non-neoplastic diseases of the pleura?
Inflammation (pleurisy, pleuritis)
- collagen vascular diseases
- pneumonia, TB
- lung infarct, usually secondary to PE
- lung tumour
Asbestos
- effusion
- fibrous plaques
- diffuse fibrosis
155
Benign tumours of the pleura are rare. Give an example
Fibroma
156
Malignant pleural tumours are common. What types of cancer are they usually?
- usually secondary adenocarcinoma (from lung, breast)
| - some rarer primary malignant mesotheliomas
157
How common is malignant mesothelioma?
2401 cases in 2007 in UK
Expected to increase to 3000 by 2020
158
What is malignant mesothelioma associated with?
More than 90% associated with asbestos exposure, blue (especially) or brown (most hazardous)
Exposure may be low level
159
What is the latent period of malignant mesothelioma?
Long latent period of 15 to 60+ years form exposure before the mesothelioma develops
160
What are the stages in the development of malignant mesothelioma?
- initial nodule and effusion
- later obliterates pleural cavity growing around the lung
- invades chest wall (pain) and lung
- nodal and distant metastases less common than carcinomas
161
What kinds of cells are in a malignant mesothelioma?
Mixed spindle and epithelioid cells - may be very fibrous (desmoplastic)
162
How would you do a differential diagnosis of malignant mesothelioma from reactive mesothelial cells?
Differential diagnosis from reactive mesothelial cells in inflamed pleura can be very difficult
163
How you do a differential diagnosis of malignant mesothelioma form adenocarcinoma?
Cellular antigen expression (immunocytochemistry on cytology or biopsy)
164
How would you treat malignant mesothelioma?
Symptomatic treatment
165
What is the prognosis for malignant mesothelioma?
Uniformly fatal in less than 1 to 3 years
166
What would you see in early malignant mesothelioma?
- small plaques on the parietal pleura
- difficult to image and biopsy
- may produce a significant pleural effusion
167
What are fibrous pleural plaques associated with?
Low level asbestos exposure
168
Where do you get fibrous pleural plaques?
On the lower thoracic wall and diaphragmatic pleural pleura
169
Do fibrous pleural plaques have a physiological effect?
- no physiological effect
- not premalignant
- seen on radiographs, a marker of possible asbestos exposure
170
Should you complete a death certificate in the case of a death from an asbestos-related lung carcinoma?
No - the death should be refried to the coroner as a possible death due to an occupational disease and no death certificate should be completed
171
When do you get a primary respiratory infection?
When you are previously healthy
172
When do you get a secondary respiratory infection?
In the case of weakened defence
173
Those with weakened defence may get a secondary respiratory infection. How might you have weakened defence?
- mucociliary escalator defects
- lowered immunity
- pulmonary oedema
174
Defects in the mucocilliary escalator may cause weakened defence leading to respiratory infection. What kind of defects may occur?
- physical obstruction eg. tumour, foreign body
- cough reflex
- ciliary dysmotility eg. Kartagener's syndrome
- mucus viscosity eg. CF
175
Lowered immunity may cause weakened defence leading to respiratory infection. Give examples
- hypogammaglobulinaemia
- lymphomas
- immunosuppressive drugs
- AIDS
- macrophage function - smoking, hypoxia
176
What causes acute bronchitis?
- viral (RSV)
- H. influenzae
- strep. pneumoniae
177
What is bronchiolitis obliterans?
Rare and life-threatening form of non-reversible obstructive lung disease in which the bronchioles are compressed and narrowed by fibrosis and inflammation
also sometimes used to refer to a particularly severe form of pediatric bronchiolitis caused by adenovirus
178
What do you get in pneumonia?
Inflammatory exudate in alveoli and distal small airways (consolidation)
179
What are the 4 different types of classification in pneumonia?
- clinical (primary or secondary)
- aetiological (bacterial, viral, fungal)
- anatomical (lobar or broncho)
- reaction (purulent, fibrinous)
180
Give the main characteristics of bronchopneumonia
- secondary (compromised defences)
- often low virulence bacteria or occasionally fungi
- common
- patchy
- bronchocentric
- resolve or heal with scarring
181
What are the characteristics of lobar pneumonia?
- primary (typically male 20-50 years)
- 90% = virulent step. pneumonia
- uncommon
- confluent segments, whole lobe or lobes with overlying pleuritis
- congestion, red then grey hepatisation, resolution without scarring
- klebsiella pneumoniae - elderly, diabetic, alcoholic
182
What causes atypical pneumonia in the non-immunosuppressed? (viral causes)
- flu
- varicella
- RSV
- rhino
- adeno
- measles
183
What causes atypical pneumonia in the non-ummunosuppressed? (bacterial causes)
- mycoplasma pneumonia (mild, chronic, fibrosis)
- chlamydia psittacosis
- coxiella burnetti (Q-fever)
- legionella pneumophila (systemic, 10-20% fatal)
184
What are the characteristic of atypical pneumonia?
- severely mild to fatal
- interstitial lymphocytes, plasma cells, macrophages
- intra-alveolar fibrinous cell-poor exudate
- diffuse alveolar damage (DAD)
185
Immunosuppressed individuals may be affected by opportunistic infection by low virulence or non-virulence organisms. Give examples
Fungi
- candida
- aspegillus
- pneumocystis carinii
Viruses
- CMV
- HSV
- measles
186
Give 3 types of non-infective pneumonia
- aspiration pneumonia
- lipid pneumoina
- cryptogenic organising pneumonia and bronchiolitis obliterans organising pneumonia (COP and BOOP)
187
What is aspiration pneumonia?
Secondary infection often with mixed anaerobes produces abscesses
188
What are the 2 types of lipid pneumonia?
- endogenous (retention pneumonitis)
| - exogenous (aspiration)
189
What causes pulmonary tuberculosis?
Mycobacterium tuberculosis
190
What is TB infection associated with?
- socioeconomic deprivation
| - immunosuppression (including AIDS)
191
What is the vaccine against TB called?
BCG
Bacille Calmette-Guerin
192
What is the fatality of TB if left untreated?
50%
193
What do you get in the TB granuloma?
Multinucleated Langhan's giant cells and caseous necrosis
194
What do atypical mycobacteria tend to infect?
Lungs with pre-existing pathology such as COPD and are more resistant to treatment than M tuberculosis
195
What is the Heaf and Mantoux test based on?
Type IV hypersensitivity to tuberculin
196
What causes pulmonary vascular diseases?
- vessel wall inflammation (vasculitis)
- obstruction of flow
- haemodynamic disturbances
197
Give 3 examples of pulmonary vasculitis (uncommon)
- necrotising granulomatous vasculitis
- goodpasture's syndrome
- microvascular damage
198
What is necrotising granulomatous vasculitis?
Wegener's granulomatosis (kidneys and nose, elevated serum ANCA)
Churg-Strauss syndrome (eosinophilia and asthma)
199
What is goodpasture's syndrome?
- anti-glomerular basement membrane antibodies
- intra-alveolar haemorrhage
- glomerulonephritis
200
Give examples of conditions that cause microvascular damage
- ARDS
- DAD (diffuse alveolar damage, seen in ARDS)
- SLE
201
Give examples of different types of embolus
- thromboemboli
- fat
- air
- amniotic fluid
- tumour
- foreign bodies
202
Explain thromboembolus
- common
| - often come from a DVT
203
What determines the symptoms in a thromboembolus? Describe the symptoms
The size of the embolus
- sudden death
- SOB
- chest pain
- pulmonary hypertension
- right ventricular failure
204
Where does a fat embolus come from?
Fat and marrow from bone fractures
205
What may cause localised obstructive pulmonary disease?
- tumour or foreign body
- distal alveolar collapse (total) or over expansion (valvular obstruction)
- distal retention pneumonitis (endogenous lipid pneumonia) and bronchopneumonia
- distal bronchiectasis (bronchial dilatation)
206
What is bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by the destruction of the muscle and elastic tissue
Results from chronic necrotising infection
207
What are the signs and symptoms of bronchiectasis?
- cough
- fever
- copious amounts of foul smelling sputum
208
Which conditions are predisposing to bronchiectasis?
- cystic fibrosis
- primary ciliary dyskinesia (Kartagener syndrome)
- bronchial obstruction: tumours, foreign body
- lupus, RA, IBD, GVHD (autoimmune diseases)
209
Bronchiectasis may be localised and therefore resectable. What are the complications of bronchiectasis?
- pneumonia
- septicaemia
- metastatic infection
- amyloid
210
Obstructive pulmonary diseases can be divided into what 2 categories?
- localised
| - diffuse
211
Obstructive pulmonary disease can be localised or diffuse. Give 2 examples of diffuse obstructive pulmonary disease
- COPD
| - asthma
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What is COPD a combination of?
Chronic bronchitis and emphysema
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What defines chronic bronchitis?
Cough and sputum for 3 months in each of 2 consecutive years
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What causes chronic bronchitis?
- chronic irritation
| - smoking and air pollution
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What is the pathology behind chronic bronchitis?
Mucus gland hyperplasia and hypertension, secondary infection by low virulence bacteria, chronic inflammation
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What do chronic inflammation of the small airways (in chronic bronchitis) cause?
Wall weakness and destruction thus centrilobular emphysema
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What is emphysema?
Abnormal permanent dilation of the airspaces distal to the terminal bronchiole, with destruction of the airspace wall, without obvious fibrosis
218
How is overinflation different to emphysema?
In just overinflation, there is no airspace wall destruction
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What are the 3 different classifications of emphysema?
- centrilobular (centiacinar)
- panlobular (panacinar)
- paraseptal (distal acinar)
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What causes centrilobular emphysema?
- coal dust
| - smoking
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What causes panlobular emphysema?
- >80% a1 antitrypsin deficient (rare, autosomal dominant)
Severest in lower lobe bases
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What do you get in paraseptal emphysema?
Upper lobe subpleural bullae adjacent to fibrosis
Pneumothroax if rupture
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What is the main symptom of emphysema?
Progressive and worsening dyspnoea
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At what age do you commonly see bronchitis vs emphysema?
bronchitis = 40-45
emphysema = 50-75
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How severe is dyspnoea in bronchitis vs emphysema?
bronchitis = mild, late in disease
emphysema = severe, early
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Describe the cough in bronchitis vs. emphysema
bronchitis = early in disease, copious sputum
emphysema = late, scanty sputum
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How common are infections in bronchitis vs emphysema?
bronchitis = common
emphysema = rare
228
How common is cor pulmonale in bronchitis vs emphysema?
bronchitis = common
emphysema = rare, terminal
229
What do you see on a chest X-ray of bronchitis vs emphysema?
bronchitis = prominent vessles, large heart
emphysema = small heart, hyperinflated lungs
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What is the stereotype for bronchitis vs emphysema?
bronchitis = blue boater
emphysema = pink puffer
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What is cor pulmonale?
Abnormal enlargement of the right side of the heart as a result of disease of the lungs or the pulmonary blood vessels
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What qualifies coal miners with chronic bronchitis and emphysema for compensation?
- >20 years underground work
- compensation depends on degree of disability and smoking history
- no CXR or history of dust exposure needed
233
What is asthma?
Chronic inflammatory disorder of the airways
- mucosal inflammation and oedema
- hypertrophic mucous glands and mucus plugs in bronchi
- hyperinflated lungs
234
What happens in a paroxysmal bronchospasm in asthma?
- wheeze
- cough
- variable bronchoconstriction that is at least partially reversible
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What are the clinicopathological classifications of asthma?
- atopic
- non-atopic
- aspirin-induced
- allergic bronchopulmonary aspergillosis (ABPA)
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What type of hypersensitivity reaction is atopic asthma?
Type I hypersensitivity reaction
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What may trigger the type I hypersensitivity reaction in atopic asthma?
- allergen (dust, pollen, animal products)
| - cold, exercise, reparatory infections
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What happens in the type I hypersensitivity reaction in atopic asthma?
- many different cell types and inflammatory mediators involved
- degranulation of IgE bearing mast cells
- histamine initiated bronchoconstriction and mucus production obstructing air flow
- eosinophil chemotaxis
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What are the persistent or irreversible changes in atopic asthma?
- bronchiolar wall smooth muscle hypertrophy
- mucus gland hyperplasia
- respiratory bronchiolitis leading to centrilobular emphysema
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Who gets atopic asthma?
Children and young adults
1 in 10 UK children diagnosed with asthma
590,000 teenagers
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9-15% of adult onset asthma is what?
Occupational
| the commonest occupational lung disease
242
What would you see on autopsy with acute asthma?
Mucus-plugged small bronchus with eosinophils
243
Is interstitial lung disease restrictive or obstructive?
Restrictive
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Interstitial lung diseases are diseases of what?
Pulmonary connective tissue (mainly alveolar walls)
245
Give 3 pathological characteristics of interstitial lung disease
- increased tissue in alveolar-capillary wall
- decreased lung compliance
- increased gas diffusion distance
246
In interstitial lung disease you get increased tissue in alveolar-capillary wall. Why?
- inflammation and fibrosis
- limited morphological patterns that differ with site and with time in any individual but with many causes and clinical associations
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What is the main feature of ACUTE interstitial disease?
Diffuse alveolar damage
Exudate and death of type I pneumocytes form hyaline membranes lining alveoli followed by type II pneumocyte hyperplasia
Histologically acute interstitial pneumonia
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What are the signs and symptoms of CHRONIC interstitial lung diseases?
- dyspnoea increasing for months to years
- clubbing
- fine crackles
- dry cough
- interstitial fibrosis and chronic inflammation with varying radiological and histological patterns
249
What is "honeycomb" lung?
Common end-stage of chronic interstitial lung disease = fibrosed honeycomb lung
250
Give some examples of chronic interstitial lung diseases
- idiopathic pulmonary fibrosis
- many pneumoconiosis (dust disease)
- sarcoidosis
- collaged vascular diseases-associated lung diseases
251
Idiopathic pulmonary fibrosis is a type of chronic interstitial lung disease. What is it also called?
Cryptogenic fibrosing alveolitis
252
What is affected first and most severely in idiopathic pulmonary fibrosis?
Sub-pleural, lower lobes
253
What is the mortality rate of idiopathic pulmonary fibrosis?
3 year = 43%
| 5 year = 57%
254
How many new cases are there are year in the UK of idiopathic pulmonary fibrosis? (in the middle aged and elderly)
5000
255
Idiopathic pulmonary fibrosis is the clinical term for which disease?
Usual interstitial pneumonia (UIP)
256
What are the histological findings in idiopathic pulmonary fibrosis/usual interstitial pneumonia?
- interstitial chronic inflammation and variably mature fibrous tissue
- adjacent normal alveolar walls
- similar pattern of fibrosis in collagen vascular disease associated interstitial lung disease and in asbestosis
257
What texture do you get on the pleural surface in idiopathic pulmonary fibrosis and why?
Bosselated "cobblestone" pleural surface due to contraction of interstitial fibrous tissue
Accentuates lobular architecture
258
What pathology do you get in sarcoidosis?
Non-caseating perilymphatic pulmonary granulomas form, then you get fibrosis
259
What parts of the body are involved in sarcoidosis?
- lungs
- hilar nodes usually involved
- other organs may be affected (skin, heart, brain)
260
What are the typical symptoms of sarcoidosis?
- tender red bumps on the skin
- shortness of breath
- persistent cough
261
Who typically gets sarcoidosis?
Typically young adult females affected, aetiology unknown
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What are the clinical findings of sarcoidosis?
- hypercalcaemia
| - elevated serum ACE
263
What are pneumoconioses known as?
The dust diseases
264
What were pneumoconioses originally defined as?
The non-neoplastic lung diseases due to inhalation of mineral dusts in the workplace
Now also includes organic dusts, fumes and vapours
265
What are the classifications of inhaled dusts that causes pneumoconioses?
- inert
- fibrogenic
- allergenic
- oncogenic (lung carcinoma and pleural mesothelioma)
266
How small must the dust particles be to reach the alveoli? (pneumoconiosis)
Less than 3 micrometers to reach the alveoli
267
Coal worker's pneumoconiosis is the severe state that develops after the milder form of the disease called what?
Anthracosis
268
What is the main pathology in coal worker's pneumoconiosis?
Progressive massive fibrosis
269
Give 2 types of coal worker's pneumoconiosis
- simple macular CWP
| - nodular CWP
270
If you have coal worker's pneumoconiosis and also over 20 years underground mining, what is it diagnosed as?
COPD
271
What is silicosis?
Type of pneumoconiosis - caused by inhaling large amounts of silica dust (sand and stone dust) usually over many years
Causes inflammation and fibrosis in the lungs
272
What is the pathology in silicosis?
Fibrosis and fibrous silicotic nodules
| nodular lesions in the upper lobes of the lungs
273
What are the other risks possible in silicosis?
- possible reactivation of tuberculosis
| - increased risk of lung carcinoma
274
What is mixed dust pneumoconiosis?
Silica with other dusts
275
What does high level of exposure to asbestos produce?
Interstitial fibrosis, in a usual interstitial pneumonia pattern
276
Abestosis is histologically like which other diseases?
- idiopathic pulmonary fibrosis
and
- collaged vascular disease associated pulmonary fibrosis
277
In asbestosis, what is identifiable in tissue sections?
Asbestos bodies
278
Asbestosis is difficult to diagnose with certainty but what is the likely incidence?
1000 cases per year in the UK
279
There is an increased risk oh which disease with asbestosis?
Lung cancer
280
Hypersensitivity pneumonitis is also known as what?
Extrinsic allergic alveolitis
281
What type of hypersensitivity reaction is hypersensitivity pneumonitis/extrinsic allergic alveolitis?
Type III hypersensitivity reaction to organic dusts
282
Give 2 examples of hypersensitivity pneumonitis and state what the allergen is
Farmer's lung - actinomycetes in hay
Pigeon fancier's lung - pigeon antigens
283
What is the pathology in hypersensitivity pneumonitis?
Peribronchiolar inflammation with poorly-formed non-caseating granulomas extended to alveolar walls
Repeated episodes leads to interstitial fibrosis
284
What are the 3 major occupational lung diseases?
- COPD in coal miners (4000 UK deaths per year)
- asbestos related lung cancer (2000 UK deaths per year)
- asbestos related malignant mesothelioma (2000 UK deaths per year)
285
What is cystic fibrosis?
An inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, GI and reproductive organs
286
What race does CF mostly affect?
Caucasians
287
What type of genetic inheritance is CF?
Autosomal recessive
288
What is the incidence of CF?
0.4 per 1000 live births
289
Cystic fibrosis is caused by a mutation in which gene?
CFTR gene
Cystic fibrosis transmembrane conductance regulator gene on chromosome 7q31.2
290
What does the CFTR gene encode?
A transmembrane chloride channel protein
291
Cystic fibrosis has a vast phenotypic variation due to what?
Variations in mutations, organ specific effects of the gene
292
What is the typical clinical presentation of a cystic fibrosis patient?
- infancy (usually)
- abnormally viscous mucous secretions
- recurrent lung infections
- failure to thrive
- recurrent intestinal obstruction
- pancreatic insufficiency
293
What are the effects of cystic fibrosis on the lungs?
- bronchioles distended with mucus
- hyperplasia of mucus secreting glands
- multiple repeated infections
- severe chronic bronchitis and bronchiectasis
294
What are the effects of cystic fibrosis on the pancreas?
- exocrine gland ducts plugged by mucus
- atrophy and fibrosis of gland
- impaired fat absorption, enzyme secretion, vitamin deficiencies (pancreatic insufficiency)
295
What are the effects of CF on the small bowel?
Mucus plugging - meconium ileus
296
What are the effects of CF on the liver?
Plugging of bile cannaliculi - cirrhosis
297
What are the effects of CF on the salivary glands?
Similar to pancreas - atrophy and fibrosis
298
95% of males with CF are what?
Infertile
299
What kind of tests can you do for CF?
- part of newborn screening in UK
- sweat test
- genetic testing
300
What is the median survival for CF in the UK?
41 years
301
What can be done to help CF patients?
- physiotherapy
- mucolytics
- heart/lung transplants
