Major diseases Flashcards
What is cystic fibrosis?
an inherited disease that causes abnormal secretions so build-up of mucus
Who does cystic fibrosis affect?
young people and 1 in 2000-3000 newborns
What causes cystic fibrosis?
autosomal recessive mutations of CFTR which is a transmembrane chloride channel found in the respiratory epithelium, exocrine ducts and sweat ducts
What does the CFTR protein do?
controls the movement of sodium and water our of the cell into the mucous layer by transporting chloride ions across the cell membrane
if it is not present or not working then chloride ions can’t flow so the mucus becomes thick and sticky
What are the two types of mutation that can occur on the CFTR protein?
homozygous or heterozygous (two different mutations one on each chromosome) result in cells producing mucus with high sodium and chloride content and viscosity that impairs mucociliary clearance
What ducts can become blocked in CF?
pancreatic ducts which can cause pancreatic damage and failure
What are the symptoms and signs of CF?
- chronic bronchial colonisation with pathogenic bacteria
- progressive bronchiectasis with small airways obstruction
there will be respiratory failure so - clubbing
- low BMI
- extensive crepitations
- obvious signs of airways obstruction
also pancreatic insufficiency leading to malabsorption and glucose intolerance
What are the major complications of CF?
- bronchiectasis
- respiratory failure
- lobar collapse
What are the tests for CF?
- postnatal tests
- measure sweat chloride concentration which will be high in CF patients
- nasal potential difference tests
How is CF diagnosed?
genetic testing for CFTR mutations
What is the treatment for CF?
- frequent antibiotics for bronchial infections
- regular physiotherapy supported by a chest clearance device
- regular use of inhaled beta-agonists
- flucloxacillin is used prophylactically against chronic s. aureus as well as azithromycin
- nebuliser DNase and hypertonic saline slows decline in lung function
What is the prognosis for CF?
death by slowly progressing type 2 respiratory failure but occasionally lung transplant is curative
What is a PE?
blockage of an artery of the lungs by a substance that has moved from elsewhere
What is acute PE?
signs and symptoms in a few hours or days
What is chronic PE?
multiple small emboli cause dyspnoea and pulmonary hypertension over weeks or months
How common is PE?
110 per 100,000, major cause of sudden death and diagnosis is often missed
What is another name for the pathogenesis of PE?
Virchow’s triad
What are the components of Virchow’s triad?
- alterations to the constituents of blood
- injury to the vascular endothelium
- changes in blood flow
What are the risk factors for PE?
- acquired altered blood constituents (malignancy, trauma, pregnancy and smoking)
- inherited altered blood constituents (antithrombin deficiency, protein S and C deficiency)
- endothelial wall damage (central venous catheter, trauma, drug use or surgery)
- altered blood flow (surgery, pregnancy and prolonged immobility)
What are the signs and symptoms of acute PE?
- dyspnoea
- pleuritic chest pain
- cough
- haemoptysis
- central cyanosis
- tachypnoea
- tachycardia
- pleural rub
- small effusion
- loud P2 on auscultation
What are the signs and symptoms of massive PE?
(associated with cardiac arrest or life-threatening shock)
- syncope
- hypotension
- severe dyspnoea
- acute right ventricular failure
- increased JVP
What are the signs and symptoms of chronic PE?
- progressive dyspnoea over weeks/ months
- sometimes with chest pain or haemoptysis
- central cyanosis in sever cases
What will be seen in a respiratory exam for massive or chronic PE?
normal respiratory exam
What does decreased oxygenation and sudden onset dyspnoea suggest?
PE
What do blood tests for PE show?
increased D-dimers due to clot breakdown but this could be raised for other reasons
What would an ABG show for PE?
type 1 respiratory failure and respiratory alkalosis
What would ECG show for PE?
sinus tachycardia, T-wave inversions in right ventricular leads
What is seen on a CXR with PE?
excludes other diseases but can’t show emboli, occasionally wedge-shaped consolidation is seen and sometimes reduced blood vessel markings and small pleural effusions
What will a VQ scan show for PE?
mismatches, normal scan means no PE but difficult to determine in patients with chronic lung disease
What is the first line test for PE?
CTPA and this also shows other lung diseases
What is the problems with angiography for PE?
invasive and highly skilled
What test can show DVT?
venous ultrasound and electrocardiography
What will echo show with massive PE?
right ventricular dilation, decreased right ventricular function or tricuspid regurgitation
What is the treatment for acute PE?
- oxygen
- analgesics for pleuritic chest pain
- fluid for hypotension
- LMWH subcutaneous for 5-7 days for anti-coagulation
- warfarin for long term
What is the treatment for massive PE?
embolectomy
What prevents recurrent PE in persistent DVT?
inferior vena cava filter
What is mortality rate for untreated PE?
30% (reduced by treatment)
What type of PE has the highest mortality?
massive PE
What increases mortality rate of PE?
- right ventricular thrombus
- history of cancer
What is pulmonary hypertension?
when mean systolic is over 25 at rest or 30 during exercise
What are the different types of pulmonary hypertension?
- primary caused by pathological processes that affect pulmonary circulation
- secondary caused by gradual changes in pulmonary circulation due to chronic lung disease
What disease leads to secondary pulmonary hypertension?
chronic hypoxic disease
What is primary pulmonary hypertension caused by and how common is it?
PE and is rare
What is the pathogenesis of pulmonary hypertension?
- increase pulmonary vascular resistance
- pulmonary venous pressure
- pulmonary vascular flow
What are the causes of pulmonary hypertension?
- thickening of pulmonary artery walls due to cell proliferation
- increased left atrial pressure
- chronic pulmonary vasoconstriction in response to hypoxia and acidosis
- loss of pulmonary vessels by scarring or alveolar wall destruction
- occlusion of pulmonary vessels
- increased pulmonary vascular flow by left to right shunt
What are the main symptoms of pulmonary hypertension?
- progressive dyspnoea on exertion
- fatigue
- chest pain on exertion because of right ventricular hypertrophy
What are the signs of pulmonary hypertension?
- raised pulmonary artery pressure so a loud P2, raised JVP with V wave
- right ventricular hypertrophy so parasternal heave and an additional S3/4
- right-sided cardiac failure so peripheral oedema, pleural effusion and tricuspid regurgitation
What is the main clinical features of pulmonary hypertension?
- unexplained SOB
- deterioration of existing lung disease with no other explanation
What is seen on an ECG with pulmonary hypertension?
this can measure pulmonary artery pressure non-invasively and shows right ventricular hypertrophy and tricuspid regurgitation
What will be seen on a CXR with pulmonary hypertension?
normal but sometimes enlarged central pulmonary arteries or other diseases that are causing the hypertension can be seen
What will a pulmonary function test show for pulmonary hypertension?
decreased transfer factor
What will a VQ scan show for pulmonary hypertension?
can find a pulmonary emboli that could be causing it
What will right heart catheterisation show for pulmonary hypertension?
accurate measure of pulmonary artery pressure but it is invasive
What is the treatment for pulmonary hypertension?
- diuretics to reduce oedema due to right heart failure
- oxygen therapy to reduce pressure by reversing hypoxia-driven vasoconstriction
- anticoagulation to prevent PE
- sever is treated with vasodilators
- surgically remove PE
What are examples of the vasodilator drugs used to treat pulmonary hypertension?
sildenafil or oral calcium channel blocker
What is the prognosis fo pulmonary hypertension?
death within five years of diagnosis
What is sarcoidosis?
an inflammatory disorder of unknown cause characterised by non-caseating granulomas
What type of disease is sarcoidosis?
type 4 hypersensitivity
How common is sarcoidosis?
5-10/100000 people
What type of person usually gets sarcoidosis?
mostly 40 year olds, more common in women
What is the pathology of sarcoidosis?
cell-mediated immunological response that causes granulomas and fibrosis in affected organs
What is the cause of sarcoidosis?
unknown cause but genetics is a known factor
What is the presentation of acute sarcoidosis?
bihilar lymphadenopathy associated with erythema nodosum, low-grade fever and arthralgia
What is the presentation of chronic sarcoidosis?
insidious onset
What are the symptoms of sarcoidosis in the lungs?
dry cough, dyspnoea and sometimes fine end respiratory crackles
What are the four stages of CXR for sarcoidosis?
1) bilateral hilar lymphadenopathy
2) parenchymal infiltrates and bilateral hilar lymphadenopathy
3) parenchymal infiltrates only
4) advanced pulmonary fibrosis
What type of diagnosis is needed for sarcoidosis?
histological diagnosis of non-caseating granulomas is needed
What are the differential diagnoses of sarcoidosis?
TB
hypersensitivity pneumonitis
fungal infection
What will be seen in a blood test for sarcoidosis?
increased serum ACE
What is an essential test for sarcoidosis?
HRCT
How do you biopsy for sarcoidosis and what will be seen in the results?
endobronchial ultrasound or biopsies of skin lesions to test for non-caseating granulomas
What is the treatment for sarcoidosis?
for severe..
- corticosteroids
- hydroxychloroquine and methotrexate
- infliximab
What is the prognosis for sarcoidosis?
acute resolves within two years but chronic can cause severe disability and occasionally death
What is pulmonary fibrosis?
a disease where the alveoli and the lung interstitium are infiltrated by mesenchymal cells and increased amounts if extracellular matrix and collagen
What does pulmonary fibrosis result in?
impaired lung function, progressive breathlessness and characteristic appearances on CXR
How common is pulmonary fibrosis?
5/100000
What type of person gets pulmonary fibrosis?
much more common in men than in women and usually presents in around 70 year olds
What is the pathophysiology of pulmonary fibrosis?
abnormal alveolar epithelium
epithelium turns to mesenchymal so there is increased production of extracellular matrix proteins so there is destruction of the lung tissue and scarring
What are the two patterns of pneumonia that are seen in people with IPF?
- interstitial pneumonia which has areas of normal lung, interstitial inflammation and honeycombing from fibroblasts and fibrotic cysts (treatment resisitant)
- non-specific interstitial pneumonia with thickening of the alveolar sputum, variable inflammation and fibrosis
What are the six causes of pulmonary fibrosis?
1) IPF (60% of patients) which is characterised by usual interstitial pneumonia
2) connective tissue disease which comes along with rheumatoid arthritis and systemic sclerosis (non-specific)
3) drugs eg chemotherapy
4) radiotherapy when pneumonitis progresses to mature pulmonary fibrosis
5) acute respiratory distress syndrome
6) other causes are hypersensitivity pneumonitis, sarcoidosis, pneumoconiosis, chronic aspiration and asbestosis
How does pulmonary fibrosis present?
progressive dyspnoea over months and a dry cough
What will be seen on examination with pulmonary fibrosis?
- finger clubbing
- reduced bilateral chest expansion
- fine late inspiratory crepitation
- cyanosis
- cor pulmonale (increased heart on right side)
What is looked for in blood tests for pulmonary fibrosis?
- rheumatoid factor, antinuclear antibodies
- creatine kinase (connective tissue disease)
- avian precipitins
- serum ACE (sarcoidosis)
What would pulmonary function test show for pulmonary fibrosis?
small lung volumes and a reduced transfer factor from the restrictive lung defect
What does imaging show for pulmonary fibrosis?
diffuse basal reticulonodular shadowing
What is seen in a HRCT for pulmonary fibrosis?
- thickened interlobular septa
- ground glass infiltration
- honeycombing
What test can help exclude other diagnoses for pulmonary fibrosis and what are these diagnoses?
bronchoscopy and bronchoalveolar lavage
to exclude sarcoidosis, hypersensitivity pneumonitis and infections
What is the treatment for pulmonary fibrosis?
(treat underlying cause)
- high dose corticosteroids
- N-acetylcysteine
- azathioprine cyclophosphamide or both
- pirfenidone or nintedanib
What can help relieve symptoms of pulmonary fibrosis?
pulmonary rehabilitation and oxygen therapy
What is the prognosis for IPF?
five year survival feat of 10-15%
connective tissue disease PF has a better prognosis
chemo or radio induced PF can be fatal or it can stop progressing
from ARDS will improve over time
What is hypersensitivity pneumonitis?
aka extrinsic allergic alveolitis
ILD caused by an immunological reaction to an inhaled antigen
What is the most common form of hypersensitivity pneumonitis?
Bird fancier’s lung
What decreases the risk of hypersensitivity pneumonitis?
smoking
What does hypersensitivity pneumonitis consist of?
type four cell-mediated hypersensivity reaction leading to fibrosis in the upper lobes
What does hypersensitivity pneumonitis present with?
- acute = breathlessness, wheeze, cough, fever and crepitations 4-6 hours after exposure
- chronic = progressive dyspnoea, cough, fatigue and weight loss
What do pulmonary function tests show for hypersensitivity pneumonitis?
restrictive or mixed restrictive-obstructive defect with reduced transfer factor
What does a CXR show for hypersensitivity pneumonitis?
acute = patchy diffuse infiltrates chronic = reticulonodular shadowing
What does HRCT show for hypersensitivity pneumonitis?
- ground glass consolidation
- centrilobular nodules
- mosaicism
- fibrotic changes
What does a biopsy show for hypersensitivity pneumonitis?
- poorly-formed small non-caseating granulomas
- mononuclear cell infiltrate
- peribronchial fibrosis
What is the treatment for hypersensitivity pneumonitis?
avoid antigen causing it if known
occasionally high dose corticosteroids work
What is the prognosis for hypersensitivity pneumonitis?
acute doesn’t damage but repeated attacks lead to chronic damage which can progress to end-stage PF
What is pneumonia?
Pneumonia is signs and symptoms of a lower respiratory tract infection with consolidation on a chest x ray
What are the different types of pneumonia?
- Lobar pneumonia is when whole lobes are infected
- Bronchopneumonia is wide-spread patches of consolidation in both lungs which is common in patients with S. aureus
- Interstitial pneumonia presents with bilateral subtle interstitial infiltrates on CXR
- Aspiration pneumonia is as a result of vomiting when drunk
How common is pneumonia?
2-5/1000 per year
Risk is higher in children under 5 and in elderly
What is the pathogenesis of pneumonia?
Inflammatory response causing the alveoli to sill with extracellular fluid
Right to left shunting of deoxygenated blood resulting in hypoxia
What is the presentation of sarcoidosis?
erythema nodosum
bilateral hilar lymphadenopathy
arthralgia
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