Week 5 RESPIRATORY PATHOLOGY Flashcards
1
Q
What is the histology of the conducting airways?
A
Pseudostratified cilliated columnar mucus secreting epithelium
2
Q
What is the histology of the alveoli?
A
Mostly flat Type I pneumocytes (gas exchange) & some rounded Type II pneumocytes (surfactant production)
3
Q
What is the partial pressure of oxygen during respiratory failure?
A
PaO2
4
Q
What is the cause of respiratory failure?
A
Due to defective:
Ventilation
Perfusion
Gas exchange
5
Q
What is Type I respiratory failure?
A
Type I (paCO2
6
Q
What is Type 2 respiratory failure?
A
(paCO2>6.3kPa)
Hypercapnic respiratory drive
7
Q
What are the general Respiratory signs & symptoms?
What does each one indicate?
There is 9
A
Sputum - Mucoid, purulent, haemoptysis
Cough - Reflex response to irritation
Stridor - Proximal airway obstruction
Wheeze - Distal airway obstruction
Pleuritic pain - Pleural irritation
Dyspnoea - Impaired alveolar gas exchange
Cyanosis - Decreased oxygenation of haemoglobin
Clubbing -
Weight loss - Catabolic state with chronic inflammation or tumours
8
Q
What do the different auscultation of respiratory examination indicate?
A
Crackles – Resisted opening of small airways
Wheeze – narrowed small airways
Bronchial breathing – Sound conduction through solid lung
Pleural rub – Relative movement of inflamed visceral & parietal pleura
9
Q
What do the different percussion of respiratory examination indicate?
A
Dull – Lung consolidation or pleural effusion
Hyperesonant – Pneumothorax or emphysema
10
Q
How common are primary benign lung tumours?
Give a example
A
Rare
Example is adenochondroma
11
Q
What percentage of primary lung cancer is carcinoma based?
A
90%
12
Q
What is the biggest risk factor of lung carcinoma?
A
cigarettes (80%)
Secondary cigarette smoke - 10-30% increase
13
Q
What are the risk factors of lung carcinoma?
A
asbestos, high level exposure, with or without asbestosis
lung fibrosis – including asbestosis and silicosis
radon
chromates, nickel, tar, hematite, arsenic, mustard gas
14
Q
What does high doses of asbestoscause?
A
High level exposure produces pulmobary interstitial fibrosis –>asbestosis
15
Q
What does asbestos look like under a ligh microscope?
A
Fibres coated with mucopolysacharide & ferric iron salts
16
Q
What is the most dangerous type of asbestos?
A
Crocidolite –> blue asbestos
17
Q
What is the least dangerous type of asbestos?
A
White asbestos (chrysotile)-
18
Q
What is Mesothelioma?
A
A cancer of mesothelial tissue, associated especially with exposure to asbestos
19
Q
What is high levels of asbestos linked to?
A
Higher incidence of all types of lung carcinoma
20
Q
what is the problem in linking asbestos to lung carcinoma?
A
Effects of smoking – multiplicative risk
Diagnosing asbestosis
Quantification of asbestos exposure
21
Q
What are the two types of lung carcinoma?
A
non-small cell carcinoma (85%)
small cell carcinoma (15%)
22
Q
Give examples of non-small carcinoma?
A
squamous carcinoma 52%
adenocarcinoma 13%
large cell neuroendocrine carcinoma
undifferentiated large cell carcinoma
23
Q
What type of cells are small cell carcinoma?
A
All are neuroendocrine
24
Q
What are neuroendocrine cells?
A
Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release hormones to the blood.
25
Give example of a Carcinoid tumours?
Low grade neuroendocine epithelial tumours
26
What is more common secondary or primary lung tumors?
Secondary
27
What is the presentation of secondary lung tumours?
Typically multiple bilateral nodules but can be solitary
28
How do you tell the difference between primary or secondary tumor?
History
Morphology
some adenocarcinomas, but not squamous
Antigen expression
Immunocytochemistry is useful but not 100% reliable
29
When performing immunocytochemistry on a patient with Lung non-mucinous adenocarcinoma & small cell
what should you identify?
cytokeratin & thyroid transcription factor positive
30
When performing immunocytochemistry on a patient with Colorectal cancer what should you identify?
cytokeratin 7 negative & cytokeratin 20 positive
31
When performing immunocytochemistry on a patient with Upper gastrointestinal tract cancer what should you identify?
Cytokeratin 7 positive & cytokeratin 20 positive
32
When performing immunocytochemistry on a patient with breast cancer what should you identify?
May be oestrogen receptor positive
33
When performing immunocytochemistry on a patient with melanoma what should you identify?
S100, HMB45, MelanA positive & cytokeratin negative
34
Where is lung carcinoma often found?
Most central, main or upper lobe bronchus (bronchogenic
35
What is the structure of Squamous carcinoma?
```
desmosomes link cells like epidermis
+/- keratinization
Occurs in ~90% in smokers
Central areas > peripheral
hypercalcaemia due to parathyroid hormone related peptide
```
36
What is bronchial normally lined with?
Lined by pseudostratified columnar epithelium with ciliated and mucus-secreting cells
37
How does Squamous metaplasia occur on the bronchial epithelium?
Irritants such as smoke cause the epithelium to undergo a reversible metaplastic change from pseudostratified columnar to stratified squamous type which may keratinize (like skin)
38
How is the first neoplastic cell produced?
One metaplastic cell undergoes irreversible genetic changes producing the first neoplastic cell
39
How does dysplasia develop?
The neoplastic cell proliferates more sucessfully than the metaplastic cells
The neoplastic clone relaces the metaplastic cells producing dysplasia
40
How does Squamous cell lung cancer (carcinoma) metastases?
Neoplastic cells breach the basement membrane producing invasive squamous carcinoma
Invading neoplastic cells infiltrate lymphatic & blood vessels to produce metastases in lymph nodes & distant sites
41
Where Adenocarcinoma in the lung develop?
It develops from mucus making cells in the lining of the airways.
42
What is expressed in many non-mucinous lung adenocarcinomas ?
Thyroid transcription factor
43
What is Bronchioloalveolar carcinoma?
A type of adenocarcinoma that has a better outlook (prognosis) than those with other types of lung cancer
44
What is the structure of Bronchioloalveolar carcinoma?
Spread of well differentiated mucinous or non-mucinous neoplastic cells on alveolar walls
45
Is Bronchioloalveolar carcinoma invasive?
Not invasive - “adenocarcinoma in situ”
46
What disease does Bronchioloalveolar carcinoma mimic?
Mimics pneumonia
47
What neuroendocrine proteins in lungs are detected by immunocytochemistry?
Neural cell adhesion molecule (CD56)
Neurosecretory granule proteins :
chromogranin, synaptophysin
48
What neuroendocrine does electron microscope detect?
Neurosecretory granules
49
What is a carcinoid tumours?
A carcinoid tumour is a rare cancer of the neuroendocrine system – the body system that produces hormones.
50
Where does carcinoid tumours grow in the lungs?
Often grow into and occlude a bronchus
51
What cells is carcinoid tumours made of?
Organoid, bland cells, no necrosis
52
What syndrome is carcinoid tumours associated with?
Associated with multiple endocrine neoplasia syndrome type 1
53
Is carcinoid tumours associated with smoking?
NO
54
What is the survival rate of carcinoid tumours and how does it spread?
Not “benign” may invade lymphatic vessels and nodes but rare distant metastases 6-9% to hilar nodes, less to distant sites, 95% 5yr survival
55
What is the difference between typical and atypical carcinoid tumours?
Typical lung carcinoids grow slowly and rarely spread to other parts of the body
Atypical lung carcinoids are much rarer, tend to grow faster and are slightly more likely to spread to other parts of the body than typical lung carcinoids
56
What percentage of lung carcinoid are atypical?
11%
57
Structure of atypical carcinoid?
Less organoid, more atypia, nucleoli - may be focal atypia in an otherwise typical carcinoid
58
What percentage of atypical carcinoid tumors metastasise and what is the survival rate?
70% metastasise
| 60% 5yr survival
59
What is the structure of Large cell neuroendocrine carcinomas?
Neuroendocrine morphology
organoid architecture, eosinophilic granular cytoplasm
antigen expression
60
What is the prognosis of Large cell neuroendocrine carcinomas? What is it assoicated with?
Prognosis similar to or worse than other non-small cell lung carcinomas
Associated with smoking
61
What is a characteristic of Small cell carcinoma?
Rapidly progressive malignant tumours
| Neurosecretory granules with peptide hormones such as ACTH
62
Is surgery possible with small cell carcinoma and why?
No because it expands very quickly
63
What is the structure of Large cell carcinomas?
No specific squamous or glandular morphology
64
What does Large cell carcinomas express?
50% express thyroid transcription factor
65
Large cell carcinomas can act as neuroendocrines, what do they express?
Express CD56 &/or neurosecretory granule proteins (synaptophysin, chromogranin)
66
What is the Paraneoplastic effects of lung carcinomas?
```
Cachexia
Skin
clubbing
Coagulopathies
Encephalomyelitis, neuropathies & myopathies
Endocrine effects
```
67
What are the endocrine effects from lung carcinomas?
Parathyroid hormone-related peptide from squamous cell carcinoma causing hypercalcaemia
ACTH and antidiuretic hormone from small cell carcinoma
5-hydroxytryptamine - carcinoid (uncommon)
68
What disease is caused by the Encephalomyelitis, neuropathies & myopathies side effects of lung carcinomas?
Lambert Eaton myasthenic syndrome due to anti-neuromuscular junction autoantibodies in small cell carcinoma
69
What happens to people skin who have lung carcinomas?
acanthosis nigricans,
| tylosis
70
How many stages are there of lung malignancy?
T1-T4
71
What stage of lung malignancy is nodules present?
T3 --> nodules present in same love
72
What stage of lung malignancy is nodules present in the othe lobe?
T4
73
At what stage does the lung malignancy invade the chest wall and diaphragm?
T3
74
At what stage does the lung malignancy invade the Heart, great vessels, trachea, esophagus and spine?
T4
75
What stage does atelectasis of whole lung occur?
T3
76
How does epidermal growth factor receptor tyrosine kinase inhibitors work?
Inhibition of EGFR TK mediated protein phosphorylation and activation of the mitotic cycle
Not curative but stabilises progression until resistance mutations develop
77
Give examples of epidermal growth factor receptor tyrosine kinase inhibitors work?
Gefitinib (Iressa) and erlotinib (Tarceva) are ATP analogues that inhibit EGFR-TK if activating mutations are present
Oral medication, less toxic than standard cytotoxic chemotherapy
78
How common are Sensitising mutations to epidermal growth factor receptor tyrosine kinase inhibitors work?
Sensitising mutations present in 10% of non-small cell lung cancers and are commoner in adenocarcinomas in non-smoking Asian women
79
How is ALK gene rearrangements detected?
| How common is it?
Detect mRNA by FISH, CISH of RT-PCR
Low expression so ICC is difficult
Present in about 10% of lung adenocarcinomas
Non-smoking, Asian, women again
80
What mutations is ALK gene rearrangements independent of?
Independent of EGFR or RAS mutations
81
What is the mutation in ALK gene rearrangements?
Variable break point inversion on short arm of chromosome 2 fuses ALK and EML
genes activating ALK tyrosine kinase.
82
What is the action of Crizotinib?
ATP analog inhibits ALK, ROS1, c-Met (Hepatocyte Growth Factor receptor /HGFR) tyrosine kinases
Temporary control – no progress or regress
83
How effective is Crizotinib?
Effective in about 90% of tumours with ALK-EML fusion gene FDA approval
84
What are the different damages to pleura?
```
Pneumothorax -----------------air
tension pneumothorax
Pleural effusion (hydrothorax)
transudate or exudate
Haemothorax -------------------blood --> due to trauma
Chylothorax --------------------lymph
Empyema (pyothorax) --------pus
```
85
What is pleura effusion?
Pleural effusion, is the build-up of excess fluid between the layers of the pleura outside the lungs.
86
Causes of pleura effusion?
```
Inflammatory:
Serous/fibrinous –exudate
Due to inflammation/infection in adjacent lung
Non inflammatory:
Congestive Cardiac Failure – transudate
```
87
How is pleura effusion diagnosed?
LDH, pH, Glucose of fluid can be measured to suggest a diagnosis
Cytology used to assess the presence of malignant or inflammatory cells
88
What diseases can cause pleuritis?
collagen vascular diseases
pneumonia, tuberculosis
lung infarct, usually secondary to pulmonary embolus
lung tumour
89
What is the effect of asbestos on pleura?
Effusion, fibrous plaques, diffuse fibrosis
90
Give example of benign Pleural tumours?
Benign - rare
| fibroma
91
What is the main cause of Malignant mesothelioma ? What is the latent period?
>90% associated with asbestos exposure, blue (especially) or brown most hazardous
Occupational, paraoccupational or environmental contamination
Exposure may be low level
Long latent period of 15 to 60+ years from exposure before the mesothelioma develops
92
What is the actions of malignant mesothelioma?
lung
Invades chest wall (pain) & lung
Nodal and distant and metastases less common than with carcinomas
Mixed spindle cell and epithelioid cells. May be very fibrous (desmoplastic)
93
What are the difficulties in diagnosing malignant mesothelioma? How do you differentiate from adenocarcinoma ?
Differential diagnosis from reactive mesothelial cells in inflamed pleura can be very difficult
Differentiate from adenocarcinoma by cellular antigen expression (immunocytochemistry on cytology or biopsy)
94
What is the prognosis and treatment of malignant mesothelioma?
Symptomatic treatment
Uniformly fatal in, usually
95
What are the presenations of Early malignant mesothelioma?
Small plaques on the parietal pleura
Difficult to image & biopsy
May produce a significant pleural effusion
96
What is Fibrous pleural plaques indication of?
Associated with low levels of exposure to asbestos
97
How does Fibrous pleural plaques present itself?
On the lower thoracic wall & diaphragmatic parietal pleura
98
What is the actions of Fibrous pleural plaques present and how is it diagnosed?
No physiological effect
Not premalignant
Seen on radiographs, a marker of possible asbestos exposure
99
What are the two types of infection?
Primary - Previously healthy
| Secondary - Weakened defence
100
What is the cause of Acute bronchitis?
Viral (RSV), H. influenzae, Strep. pneumoniae
Croup
Exacerbations of COAD
101
What is the profile of Bronchiolitis ?
Common in the young
Primary acute in infants, RSV, rare, resolve or develop bronchopneumonia
Follicular bronchiolitis
Bronchiolitis obliterans
102
What is pneumonia?
Inflammatory exudate in alveoli & distal small airways - consolidation
103
What are the different classifications of Pneumonia?
Clinical - primary or secondary
Aetiological - Bacterial, viral, fungal
Anatomical - lobar pneumonia or bronchopneumonia
Reaction - purulent, fibrinous
104
What is the profile of Bronchopneumonia?
```
Secondary - compromised defences
Often low virulence bacteria or occasionally fungi
Common
Patchy
Bronchocentric
Resolve or heal with scarring
```
105
Who is at risk of Lobar pneumonia? What is its cause?
Primary - typically male 20 to 50 years
90% - virulent Strep pneumoniae
Uncommon
106
What are the actions of Lobar pneumonia?
Confluent segments, whole lobe or lobes with overlying pleuritis
Congestion, red then grey hepatisation, resolution without scarring
107
What are the Non-immunosuppressed causes of atypical pneumonia?
Viral - flu, varicella, RSV, rhino, adeno, measles
Mycoplasma pneumoniae - Mild, chronic, fibrosis
Chlamydia (psittacosis), Coxiella burnetti (Q-fever)
Legionella pneumophilla - Systemic, 10- 20% fatal
108
What are the actions of Non-immunosuppressed causes of atypical pneumonia?
Severity mild to fatal
Intersitial lymphocytes, plasma cells, macrophges
Intra-alveolar fibrinous cell-poor exudate
Diffuse alveolar damage (DAD)
109
What kind of people have immunosuppressed atypical pneumonia?
People who have Lymphomas, medication, AIDS
110
What y low virulence or non-virulent organisms can cause atypical pneumonia in people who are immunocompromised?
Fungi - candida, aspergillus, Pnumocystis carinii
| Viruses - CMV, HSV, measles
111
Give examples of non infective pneumonias?
Aspiration pneumonia
Secondary infection often with mixed anaerobes produces abscesses
Lipid pneumonia
Endogenous – retention pneumonitis
Exogenous – aspiration
Cryptogenic organising pneumonia & bronchiolitis obliterans organising pneumonia (COP & BOOP)
112
What is the cause of Pulmonary tuberculosis and where it is commonly found in the body?
Mycobacterium tuberculosis
| Lung is the commonest site of infection
113
What is the association of Pulmonary TB?
Socioeconomic deprivation
| Immunosuppression - including AIDS and transplant patients
114
What are the treatments of pulmonary TB?
Bacille Calmette-Guerin (BCG) vaccine
| Antituberculous drugs & multidrug resistance
115
What is the sequence of events in Pulmonary tuberculosis ?
Primary infection - Asymptomatic, Ghon complex in peripheral lung & hilar nodes, usually resolves
Reactivation - usually apical
Resolution or progression - empyema, pneumonia, miliary or more limited spread to other organs - bone, kidney
Scarring - fibrous calcified scar
116
What are the diffrent types of emboli?
Thromboemboli
Fat emboli - fat & marrow from bone fracture
Air - due to medical error
Amniotic fluid
Tumour
Foreign bodies --> IV drug users and there needle snap off and get embolism
117
Give example of a localised obstructive pulmonary diseases
Distal retention pneumonitis (endogenous lipid pneumonia) and bronchopneumonia
Distal bronchiectasis (bronchial dilatation
118
What is the consequence of localised obstructive pulmonary diseases?
Tumour or foreign body
| Distal alveolar collapse (total) or over expansion (valvular obstruction)
119
What is Bronchiectasis?
Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue
120
How common is Bronchiectasis?
Rare due to antibiotics
121
What is the cause and site of Bronchiectasis?
Results from chronic necrotizing infection
| Site: Bronchus/bronchioles
122
Signs and symptoms of Bronchiectasis?
Cough, fever, copious amounts of foul smelling sputum
123
What are predisposing conditions to Bronchiectasis?
Cystic fibrosis
Primary ciliary dyskinesia, Kartagener syndrome
Bronchial obstruction: tumour, foreign body
Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD
124
What is the treatment and complications of Bronchiectasis?
Treatment --> retractable
| Complications --> pneumonia, septicaemia, metastatic infection, amyloid
125
Give two example of diffuse obstructive pulmonary disease?
Chronic obstructive pulmonary disease
| Asthma
126
What is COPD a combination of?
A combination of chronic bronchitis & emphysema
127
What is site and cause of Chronic bronchitis?
Site: Bronchus
Cause : Chronic irritation
Smoking & air pollution
Middle aged & old
128
What is chronic bronchitis?
cough & sputum for 3 months in each of 2 consecutive years
129
What is the pathology of chronic bronchitis?
Mucus gland hyperplasia and hypersecretion, secondary infection by low virulence bacteria, chronic inflammation
130
What is the result of chronic bronchitis?
Chronic inflammation of small airways of the lung causes wall weakness & destruction thus centrilobular emphysema
131
What is emphysma?
Abnormal permanent dilation of airspaces distal to the terminal bronchiole, with destruction of airspace wall, without obvious fibrosis
132
What are the different types of emphysma? Indicate the cause of each of them
Centrilobular (centiacinar) Coal dust, smoking
Panlobular (panacinar) - >80% a1 antitrypsin deficient (rare, autosomal dominant) , severest in lower lobe bases
Paraseptal (distal acinar) - Upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if rupture
133
Site and symptoms of emphysma?
Acina is the site
| Symptoms : Dyspnoea: progressive and worsening
134
For the COPD to be predominantly bronchitis or emphysma what age would the COPD come?
40-50 then its predominantly bronchitis
| 50-75 then it's predominantly emphysma
135
What is the Stereotype of Predominant Emphysema and Predominant bronchitis?
Pink puffe and Blue bloater respectively
136
What does chest xray show if COPD is Predominant Emphysema or Predominant bronchitis
Small heart, hyperinflated lungs
| or Prominent vessels, large heart
137
What is asthma?
Chronic inflammatory disorder of the airways
138
What are the symptoms of asthma?
Paroxysmal bronchospasm
Wheeze
Cough
Variable bronchoconstriction that is at least partially reversible
139
What is the consequence of asthma on the lungs?
Mucosal inflammation & oedema
Hypertrophic mucous glands & mucus plugs in bronchi
Hyperinflated lungs
140
What are the Clinicopathological classification of asthma?
Atopic , non-atopic, aspirin-induced, allergic bronchpulmonary aspergillosis (ABPA)
141
What is the patholopy of atopic asthma caused by Type I hypersensitivity reaction?
Allergen - dust, pollen, animal products
Cold, exercise, reparatory infections
Many different cell types and inflammatory mediators involved
Degranulation of IgE bearing mast cells
histamine initiated bronchoconstriction & mucus production obstructing air flow
eosinophil chemotaxis
142
What are the Persistent or irreversible changes of atopic asthma?
bronchiolar wall smooth muscle hypertrophy
mucus gland hyperplasia
respiratory bronchiolitis leading to centrilobular emphysema
143
What group of people most likely to get atopic asthma?
Kids and young adults
144
What is Interstitial lung disease?
```
Very heterogenous group
Usually diffuse and chronic
Diseases of pulmonary connective tissue
Mainly alveolar walls
Restrictive rather than obstructive lung disease
```
145
What happens to the alveolar walls in interstitial lung disease?
Increased tissue in alveolar-capillary wall
Inflammation & fibrosis
Limited morpholgical patterns that differ with site and with time in any individual but with many causes & clinical associations
146
What is the effect of interstitial lung disease on lung performance?
Decreased lung compliance
Increased gas diffusion distance
147
What is Acute interstitial disease?
Diffuse alveolar damage – exudate & death of type I pneumocytes form hyaline membranes lining alveoli followed by type II pneumocyte hyperplasia. Histologically acute interstitial pneumonia
148
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
Common end-stage fibrosed “honeycomb lung”
149
Examples of Chronic interstitial lung diseases?
idiopathic pulmonary fibrosis,
many pneumoconioses (dust diseases)
sarcoidosis,
collagen vascular diseases-associated lung diseases
150
What is the profile of Sarcoidosis?
Non-caseating perilymphatic pulmonary granulomas, then fibrosis
Hilar nodes usually involved
Other organs may be affected- skin,heart, brain
Hypercalcaemia & elevated serum ACE
Typically young adult females, aetiology unknown
151
What is Pneumoconioses?
The dust disease --> The non neoplastic lung diseases due to inhalation of mineral dusts, organic dusts, fumes and vaporation in work place
Occupational disease
152
What are the different types of inhaled dust that can cuase Pneumoconioses?
inert
fibrogenic
allergenic
oncogenic
lung carcinoma & pleural mesothelioma
153
What causes Silicosis?
Silica - sand & stone dust
154
What is the pathology of Silicosis?
Kills phagocytosing macrophages
Fibrosis & fibrous silicotic nodules, also in nodes
Possible reactivation of tuberculosis
155
What is silicosis?
Lung fibrosis caused by the inhalation of dust containing silica.
156
What is Mixed dust pneumoconiosis?
Silica with other dusts
157
What is the Asbestosis?
High level exposure of asbestos produces interstitial fibrosis, in a usual interstitial pneumonia pattern
158
What is the histological difference beteen Asbestosis and idiopathic pulmonary fibrosis or collagen vascular disease associated pulmonary fibrosis ?
Asbestos bodies are identifiable in tissue sections of asbestosis
159
What does Asbestosis increase the risk of?
Increased risk of lung cancer with asbestosis and with high asbestos exposure but no fibrosis
160
What is Hypersensitivity pnumonitis?
aka extrinsic allergic alveolitis
161
What type of hypersensitive reaction is Hypersensitivity pnumonitis?
Type III hypersensitivity reaction organic dusts
farmers’ lung - actinomycetes in hay
pigeon fanciers’ lung - pigeon antigens
Peribronchiolar inflammation with poorly formed non-caseating granulomas extends alveolar walls
Repeated episodes lead to interstitial fibrosis
162
What is CF?
An inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive organs
163
Who does Cf most affect and what is the pathology of CF?
Mostly affects Caucasians
Incidence 0.4 per 1000 live births
Autosomal recessive inheritance
Mutation in CFTR gene
(Cystic fibrosis transmembrane conductance regulator gene on chromosome 7q31.2 )
Vast phenotypic variation due to variations in mutations, organs specific effects of the gene
Gene encodes a transmembrane chloride channel protein
164
What are the general clinical presentation of CF?
Clinical presentation: Infancy (usually)
```
Abnormally viscous mucous secretions
Recurrent lung infections
Failure to thrive
Recurrent intestinal obstruction
Pancreatic insufficiency
```
165
What is the affet of Cf on the lung?
Bronchioles distended with mucus
Hyperplasia mucus secreting glands
Multiple repeated infections
Severe chronic bronchitis and bronchiectasis
166
What is the affet of Cf on the pancreas?
Exocrine gland ducts plugged by mucus
Atrophy and fibrosis of gland
Impaired fat absorption, enzyme secretion, vitamin deficiencies ( pancreatic insufficiency
167
What is the affet of Cf on other organs?
Small bowel: mucus plugging - meconium ileus
Liver: plugging of bile cannaliculi – cirrhosis
Salivary glands: Similar to pancreas: artophy and fibrosis
95% of males are infertile
168
How is CF diagnosed?
Part of Newborn screening in UK
Sweat test
Genetic testing
169
What is the treatment for CF?
Median survival 41 years in the UK
Physiotherapy
Mucolytics
Heart/lung transplants
