Respiratory system Flashcards
1
Q
Mycobacteria and TB: mycobacterium TB facts
A
- 2-4 μ by 0.2-0.5 μ
- Obligate aerobe: well-aerated upper lobes
- Facultative intracellular parasite: usually macrophages - because it’s made up of a lot of lipids so can grow inside the macrophages without being killed
- Slow generation time
15-20 h
M.bovis from cattle
2
Q
Mycobacteria and TB: Where does TB most commonly affect?
A
Lungs - pulmonary TB but can also affect the lymph nodes, bones, joints and kidneys and it can cause meningitis
3
Q
Mycobacteria and TB: How does TB spread and who is more likely to affect?
A
TB is most commonly spread in droplets being coughed or sneezed into the air
Frequent or close prolonged contact with an infected person is necessary
People with already weakened immune system
4
Q
Mycobacteria and TB: Who are the at risk groups of TB?
A
HIV infection
Steroids, chemotherapy, transplants, elderly
Unhealthy, over-crowded conditions
Stay in high-rate country- S.E. Asia, sub-Saharan Africa, parts E.Europe
Those exposed to TB in youth
Children of parents from high-rate countries
Prisoners, drug addicts, alcoholics
Malnourished
5
Q
Mycobacteria and TB: Where and how does primary TB start?
A
Droplet nuclei inhaled
Taken up by alveolar
macrophages – not
activated (lipids)
Droplet nuclei (c.5 μ) reach the alveoli where the infection begins
Granuloma in lung = Ghon focus
Enlarged lymph nodes + GF = Primary Complex
—> mild flu like symptoms
6
Q
Mycobacteria and TB: how does secondary TB occur?
A
Reactivation of dormant mycobacteria when something happens to the T cells: impaired immune function
Reinfection in a person previously sensitised to mycobacterial antigens
- occurs months, years or decades after primary infection
- reactivation most commonly occurs at apex of lungs - highly oxygenated
7
Q
Mycobacteria and TB: What is the mechanism of secondary TB?
A
- Caseous centres of tubercles liquefy
- Organisms grow very rapidly in this
- Large Ag load
- bronchi walls become necrotic and rupture
- cavity formation
- organisms spill into airways and spread to other areas of lung: highly infectious
- Primary lesions heal
- Ghon complex, Simon foci
8
Q
Mycobacteria and TB: What is milliary TB?
A
rapid dissemination of th organism
9
Q
Mycobacteria and TB: How do you classify a TB infection (not lung disease) LEARN
A
Organism present Tuberculin skin test positive Chest X-ray normal Sputum smears negative Sputum culture negative No symptoms Not infectious Not defined as a case of TB
Only 3-4% of those infected develop active disease upon initial infection, 5-10% within one year
10
Q
Mycobacteria and TB: How do you classify a TB lung disease? LEARN
A
Organism present Tuberculin skin test positive Lesion on chest X-ray Sputum smear positive Sputum culture positive Symptoms Infectious Defined as a case of TB
11
Q
Mycobacteria and TB: What are the most common symptoms?
A
Cytokines (TNF, IL-3, GM-CSF) Persistent cough, +/- sputum Anorexia Weight loss Swollen glands (usually in the neck) Fever Night sweats Sense of tiredness and being unwell Coughing up blood
can’t really diagnose from symptoms
12
Q
Mycobacteria and TB: What is the standard recommended regimen?
A
Isoniazid, rifampicin, pyrazinamide and ethambutol
for two months followed by isoniazid and rifampicin for four months
Trying to treat without the organism becoming resistant to the antibiotic, that’s why there is a standard regime
13
Q
Mycobacteria and TB: Why is there a standard recommended regimen?
A
Prevent spread of MDR-TB standardized drug regimens directly observed treatment (DOT) good supply of high quality drugs isolation of infectious patients - negative pressure isolation room
14
Q
Mycobacteria and TB: What role does vitamin D play in TB?
A
Vitamin D has role in activating macrophages to destroy mycobacteria
Often a vitamin D deficiency in ethnic populations in UK
15
Q
Mycobacteria and TB: What is the timeline of treatment of TB?
A
Non-infectious after c. 2 weeks
Begin to feel better after 2-4 weeks
Treatment must continue for 6 months + - must prevent resistance developing
Longer treatment for TB meningitis or if TB is resistant
16
Q
Mycobacteria and TB: What are the fatality rates?
A
Untreated TB - 40 to 60%
Treated TB
- 5 to 50%
- depending on nutrition; quality and availability of medical care; HIV status
17
Q
Mycobacteria and TB: What is the BCG vaccine and how does it affect the skin test?
A
Protection restricted to childhood tuberculosis which is rarely infectious
No impact on HIV-related TB
Does not prevent infection – only disease
Invalidates tuberculin skin test
Therefore – targeted vaccination; effective for about 15 y
18
Q
Mycobacteria and TB: what is the link between TB and HIV?
A
HIV / AIDS and TB are overlapping epidemics – “the unholy alliance”
- Worldwide 30-80% of AIDS patients get TB
HIV increases risk of acquiring TB
Destroys immune system
TB makes HIV worse
Increases replication rate of HIV
TB treatment slows down HIV and keeps patients alive to get HIV drugs
19
Q
Mycobacteria and TB: What are the obstacles to TB control?
A
Lack of financial resources- half of all cases in China, Indonesia, India, Pakistan and Bangladesh
Social instability - e.g. Russia
HIV epidemic
- HIV/AIDS doubles the TB death rate
- 30 to 70% of TB cases in Africa are HIV positive
- reinfection in South Africa
Drug resistance
Stigma
20
Q
Mycobacteria and TB: What do skin tests do?
A
Heaf, Tine, Mantoux
- ascertains infection rather than disease
- may be negative in severe TB or concomitant HIV, malnutrition, steroids
- may be positive with BCG or after exposure to environmental mycobacteria
21
Q
Mycobacteria and TB: What are T- SPOT TB & QuantiFeron gold?
A
Blood tests to replace tuberculin tests
Detect reactive T cells - specific for mycobacterium TB, not for BCG
Specific for Mtb
Not BCG
22
Q
Mycobacteria and TB: How is microscopy used to look at TB sputum?
A
Ziehl-Neelsen stain: Needs > 10,000 organism/ml at 100X lens
or flourescent
Rhodamine-Auramine is more sensitive
One-third of pulmonary TB (two-thirds extra-pulmonary) undiagnosed by microscopy
23
Q
Mycobacteria and TB: How do you culture TB sputum?
A
Homogenise (Sputasol - breaks it down)
Decontaminate (4% NaOH Petroff) - kills all bacteria but the mycobacterium
Concentrate (centrifugation)
(Middlebrook’s medium)
Löwenstein-Jensen medium
4-6 weeks for visible colonies
(Liquid media; Kirchner’s)
24
Q
Mycobacteria and TB: how does automatic culturing work?
A
MGIT 960
- Fluorescent reaction quenched by O2
- Growth of mycobacteria lifts quenching and tubes fluoresce
- 10 days
another test - MPT64 - antigen ONLY given off by TB so this test is done afterwards
25
Mycobacteria and TB: Look at nucleic acid detection tests again -
MTB complex - rifampicin resistance genes
26
Mycobacteria and TB: how is typing carried out?
Spoligotyping
- Variable Number of Tandem Repeats
- Mycobacterial Interspersed Repetitive Units
- VNTR-MIRU
- e.g. VNTR 84455 MIRU 244428223533
17 digit profile given - fingerprint of that organism so can track the infection
27
Respiratory viruses and atypical pathogens: Why are some viruses restricted to infecting certain areas?
expression of different types of cell expressed receptors.
28
Respiratory viruses and atypical pathogens: What are the types of infection? and the two types of invaders?
Surface: - local spread
- short incubation
e. g. common cold, Candida
Systemic: - spreads from mucosal site of entry to other site in the body
- returns to surface for final shedding stage
- longer incubation: weeks
- e.g. measles, mumps, rubella
Professional invaders:- infect healthy respiratory tract
Secondary invaders: - infect compromised tract
29
Respiratory viruses and atypical pathogens: What is Rhinitis and sinusitis?
The common cold
Caused by various viruses
Transmission by aerosol
Self-limiting (surface infections) and not systemic in healthy people
Identification usually not necessary unless clinical symptoms worsen- Involvement of LRT.
Molecular methods most common for ID, epidemiololgical info only
no vaccines - viruses change regularly and many of them cause the same symptoms
30
Respiratory viruses and atypical pathogens: How do viruses cause the classic cold symptoms?
Virus adheres to ciliated epithelium and avoids flushing out
Then enters cells and replicates inside cells, this cell damage leads to release of the clear runny nose fluid.
And leads to activation of host defenses release of cell debris and transient damage to ciliated epithelium.
Then there is an immune response that might be accompanied by overgrowth of normal flora and finally recovery and regeneration of ciliated epithelium.
31
Respiratory viruses and atypical pathogens: Describe the structure of an adenovirus
Icosohedral symmetry, non-enveloped-resistant to desiccation
Attach via the adhesins on end of penton fibres
dsDNA
32
Respiratory viruses and atypical pathogens: What is pharyngitis and tonsillitis mostly caused by?
70% caused by virus
A common complication of common colds due to surrounding infections
Also site of entry of EBV (Herpes lecture) and Mumps virus (before dispersal around body)
33
Respiratory viruses and atypical pathogens: What is mumps?
Paramyxovirus
Air-borne spread (saliva etc.)
Commonly spread and contracted in school age children
Most children now vaccinated- M(easles)M(umps)R(ubella)
MMR fear increased occurrence in UK for a number of years
Complications include Orchitis- Inflammation of the Testicles- PAINFUL especially in adult men
34
Respiratory viruses and atypical pathogens: What is laryngitis and tracheitis often caused by?
Often caused by parainfluenza viruses, adenovirus and influenza
Burning pain in the larynx and trachea
Can become obstructed easily in children- croup. Specific type of cough with Stridor inhalation
35
Respiratory viruses and atypical pathogens: What is bronchitis and bronchiolitis caused by?
Several viral causes: Rhinoviruses, coronaviruses (SARs), adenoviruses and influenza
Atypical pathogens: Mycoplasma pneumoniae
Many secondary infections- especially in children- narrow airways- leading to bronchiolitis- and pneumonia
75% of bronchiolitis caused by Respiratory Syncytial Virus
36
Respiratory viruses and atypical pathogens: What is RSV respiratory syncytial virus? (type of bronchiolitis)
Aerosol and hand-hand/ surfaces transmission
Pathology creates large fused cells (Syncytia)
Outbreaks in winter months
Nearly all children have been infected by age 2- but often nothing more serious than common cold
Severe in young infants- peak mortality 3 months of age (why?)
Infants: Cough, cyanosis, rapid respiratory rate: pneumonia and bronchiolitis
Older children and adults is more like a common cold.
Treatment supportive- hydration- bronchiodilators
Severe cases require ribavirin antiviral or Palivizumab-prophylactic in at risk groups (e.g. prem babies at risk (heart defect, lung disease, immunodef., in season)
VACCINE IMMINENT IN NEXT FEW YEARS
37
Respiratory viruses and atypical pathogens: What is Orthomyxoviridae? (influenza virus)
Transmitted by aerosol droplet
Occurs worldwide- restricted to coldest months of year
Initial infection: virus attaches to sialic acid receptors on epithelial cells via viral HA protein (quite non specific, on almost every cell in the respiratory tract so can affect the whole tract)
1-3 days: liberated cytokines result in systemic chills, malaise, fever and muscle aches, runny nose and cough
Usually recover after 1 week, but some develop pneumonia and bronchitis and have lingering symptoms.
Secondary invaders can cause lethal infections: pneumococci, staphylococci
38
Respiratory viruses and atypical pathogens: What is the structure of influence virus?
Two surface glycoproteins:
HA- Haemagglutinin
NA- Neuraminadase
Host-derived viral envelope
ssRNA genome: 8 segments
Nucleoprotein and polymerases
39
Respiratory viruses and atypical pathogens: What do HA and NA glycoproteins do? (look over viral uptake of HA slide 16)
major antigens
HA: major antigenic determinant
- HA binds sialic acid receptors on epithelial cell surface
- Major source of antigenic variation
NA : second antigen determinant
- Involved in release of the virus from host cells during budding
40
Respiratory viruses and atypical pathogens: What are the 3 types of influenza?
A: Yearly epidemics and occasional serious worldwide epidemics- important animal reservoirs in birds and pigs
B: yearly epidemics- no animal reservoir
C: minor respiratory illness- no epidemics
41
Respiratory viruses and atypical pathogens: How is influenza classified?
H- antigen (HA):
- 16 Avian and mammalian types
- Only 3 are human adapted (H1-3) - transmitted within humans
N-antigen (NA):
9 known serotypes
2 human adapted (N1-2)
42
Respiratory viruses and atypical pathogens: What is antigenic drift?
Small point mutations in HA and NA that accumulate in population over time (mutations usually occur in the antigenic parts of them molecule which prevents antibody binding)
Result in new variant viruses that can re-infect individuals
Source of yearly flu epidemics worldwide
43
Respiratory viruses and atypical pathogens: How are the yearly flu vaccines produced?
Vaccine strains chosen in
February for northern hemisphere
Strains grown in embryonated hen eggs: not applicable to individuals with Egg allergy
Formalin killed, detergent treated viral ‘split’ vaccines
Southern hemisphere strains used to predict next years northern strains- yearly vaccines of at-risk (current dominant strains are H3N2-types)
Vaccine contains one H3N2 strain, one H1N1 and one B strain
Administered in October each year
44
Respiratory viruses and atypical pathogens:How does influenza A go through antigenic shift?
Less common
Results in major shift in viral composition
Major gene reassortment resulting in new HA and NA types
Little immunity in population
CAUSE OF MAJOR WORLD PANDEMICS
Only influenza A
45
Respiratory viruses and atypical pathogens: What are the features of pneumonia?
Many organisms cause identical symptoms
Only organisms less than 5mm can enter the alveoli
Often secondary to preceding damage- Cystic Fibrosis or influenza
Influenced by Immunocompromisation
- e.g. HIV and pneumocystis infections
Children:
- mainly viral causes – RSV, parainfluenza
- secondary bacterial infections
Neonates may acquire Chlamydia from mother in birth
Adults:
Bacterial causes more common-: e.g. Strep. Pneumoniae formerly most common (Prof Douglas lecture)
46
Respiratory viruses and atypical pathogens: What is atypical pneumonia?
Term originally coined as pneumonia caused by Penicillin resistant organisms
‘Walking pneumonia’- not hospitalised
Typically report chest pain, cough, shortness of breath
- less serious symptoms compared to normal pneumonia
Mainly caused by :
Mycoplasma pneumoniae
Chlamydophila (formerly Chlamydia)
Legionella pneumophila
47
Respiratory viruses and atypical pathogens: What is mycoplasma pneumoniae?
Very small bacterium with minimalist genome (0.5Mbp)- possibly smallest of any free-living organism in nature (Ventner)- made artificially- SYNTHIA (related spp.)
No peptidoglycan- cholesterol- penicillin resistant…
‘walking’ pneumonia- sick but not hospitalised
Major cause of pnuemonia in young adults and students
Efficient binding to cilial epithelial cells (sialic acid) via a special cytadherence organelle rich in a cytadhesin (P1) for sialic acid rich glycolipids.
48
Respiratory viruses and atypical pathogens: What is chlamoydophila pneumoniae?
Small, obligate Gram-negative intracellular pathogen
Complex life-cycle:
- Elementary body- akin to a spore
- Reticulate body- intracellular growth and replication
No peptidoglycan (Pen resistant therefore)
Flu-like illness
Detection by ELISA or MicroImmunofluorescence
Related C. psittaci from parrots
49
Respiratory viruses and atypical pathogens: What is legionnaires disease
Causes by Legionella pneumophila
Motile aeerobic Gram-negative rod
Isolation on BCYE medium (Buffered Charcoal Yeast Extract)
Urinary antigen test - antigens from the bacteria are processed into the urine but not the bacteria
Pneumonia symptoms often accompanied by neurological presentations such as confusion
No human-human transmission
Acquired from environmentally derived aerosols
Air-conditioning, Spa-baths, Hot-air heating, shower systems, cooling tower reservoirs
Commonly in hospitals, high rise blocks, hotels, student residences, factory air-con sources
Ubiquitous in environment (symbiosis with amoeba)
Intracellular invader of phagosomes and lung cells
50
Resp disorders and management: How do you diagnose emphysema/ COPD?
Spirometry - FEV1/FVC less than 70%
51
Resp disorders and management: What are the symptoms of COPD?
Chronic
SOBOE
Wheeze
Cough
Weight loss
Acute/Exacerbation
Acute sob/wheeze
Worsening sputum production
Fever
Drowsiness/CO2 narcosis
52
Resp disorders and management: What are the signs of COPD?
```
Cachexia
Use of accessory muscles
Pursed lips
Cyanosis
CO2 flap
Drowsiness in CO2 narcosis
```
53
Resp disorders and management: What might you see on examination of COPD?
Hyper-expanded chest
Hyperesonant - tapping on chest, hollow sound
Reduced breath sounds
Wheeze
Elevated JVP & peripheral oedema in late disease
54
Resp disorders and management: What are the different clinical parameters of COPD disease severity?
Lung function
Symptoms (e.g. COPD Assessment Test)
Exacerbation frequency
BODE Index
55
Resp disorders and management: What are the correct symptoms and signs to diagnose COPD?
older than 35, history of smoking and at least one of the following exertional breathlessness, chronic cough, regular sputum production, frequent winter bronchitis, wheezing
56
Resp disorders and management: What is haemoptoysis the number one cause of?
Infection
57
Resp disorders and management: What co-morbidities are common for someone with COPD?
Cardiovascular disease, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression/ anxiety, lung cancer
58
Resp disorders and management: What are the treatment aims of COPD?
Reduce symptoms
reduce exacerbations
improve lung function
reduce mortality
59
Resp disorders and management: What are the NICE guidelines for copD treatment?
Offer treatment and support to stop smoking
offer pneumococcal and influenza vaccinations
offer pulmonary rehabilitation if indicated
co-develop a personalised self management plan
optimise treatment for co-morbitiies
then talk about inhalers
60
Resp disorders and management: What is Roflumilast?
helps for patients with a lot of exacerbations
diarrhoea, weight loss, nausea, insomnia etc
61
Resp disorders and management: What do mucolytics do?
lyse mucous - decrease mucous
| warning about side effects with theophyllines
62
Resp disorders and management: what is LTOT?
Minimum 14hours per day of continuous O2 therapy delivered by concentrator
Has prognostic benefit
MORTALITY BENEFIT
63
Resp disorders and management: How can you prevent exacerbations?
Seasonal Influenza vaccination (one-off pneumococcal vaccination)
Inhaled steroids (in conjunction with LA bronchodilator)
Other agents
- Anticholinergics – ipratropium/tiotropium
- Mucolytics (carbocysteine)
Pulmonary Rehabilitation (used for symptom control as well)
64
Resp disorders and management: What is asthma?
More inflammation, more smooth muscle - narrow diameter to airways?
65
Resp disorders and management: What are the signs of asthma on examination?
```
Elevated respiratory rate
Inability to complete sentences
Peripheral/Central cyanosis
Audible wheeze
Tachycardia
```
66
Resp disorders and management: What are the signs of asthma on examination?
```
Elevated respiratory rate
Inability to complete sentences
Peripheral/Central cyanosis
Audible wheeze
Tachycardia
Eczema
Nasal polyps
Cushingoid - too much steroid
```
```
Exacerbation
Assess RR
Heart rate
SpO2
Ability to speak
```
67
Resp disorders and management: What are the symptoms of asthma?
```
Wheeze
Cough
Chest tightness
Dyspnea
Nocturnal
```
```
Possible triggers
Exertion
Dust
Change in temperature
Emotional situations
Occupation
```
68
Resp disorders and management:What is Omalizumab?
Antibodies against IGE
atopic asthma
Allergic history to aeroallergens
poor lung function
69
Resp disorders and management: How is IL5 involved in reducing exacerbation frequency of asthma?
Involved in bone marrow eosinophil maturation
transfer from bone marrow to blood supply
translocation and migration from systemic circulation to lung tissue
implicated in eosinophil activity and exacerbations
70
Resp disorders and management What is the ratio of NSCLC and SCLC?
85% NSCLC
15% SCLC
Risk of spread from primary tumours to nodes and distal organs (bone,liver, lung pleura cavity)
71
Resp disorders and management: What % of lung cancers are operable at diagnosis?
10%
72
Resp disorders and management: What are the major subtypes of NSCLC?
Squamous Cell
Adenocarcinoma
Adenocarcinoma in situ (aka bronchoalveolar carcinoma)
73
Resp disorders and management: What chest symptoms do you get with lung cancer?
Sob – lobar collapse, effusion, lymphangitis
Chest pain – rib involvelement, chest wall invasion
Cough
Haemoptysis – usually due to endobronchial involvement
74
Resp disorders and management: What constitutional symptoms do you get with lung cancer?
Weight loss
Low appetite
Low energy levels
75
Resp disorders and management: What paraneoplastic syndromes are there?
High calcium (PTH release or bone involvement) – nausea, confusion, abdo pain & constipation
SIADH – confusion, fits, lethargy
Hypertrophic pulmonary osteoarthropathy
Lambert Eaton Syndrome - neuromuscular weakness - problems with NM junction
76
Resp disorders and management: Where are the common metastases for lung cancer?
SVCO due to mediastinal disease
Brain mets – confusion, nausea, headache
Bone mets- path fracture, pain
Liver mets – abdo pain
77
Resp disorders and management: What are the signs of lung cancer?
```
Finger nail clubbing
Cachexia
Horner’s syndrome
Neck nodes
Chest signs
Palpable liver
SVCO
```
78
Resp disorders and management: how is lung cancer diagnosed?
```
CXR:
Cheap
Good screening tool
Won’t detect mediastinal disease necessarily
Won’t detect small nodules
Not a staging tool
```
CT
Staging tool
Detailed information
Requires IV contrast
Contrast not allowed in patients with CKD
Cannot detect microscopic disease e.g. in med nodes
```
PET scan for radical treatable disease
Infusion of FD Glucose
Detects cancer, infection and vasculitis
Very sensitive
Expensive
False positive rate
Care needed in DM
```
```
Tissue biopsy
Image guided (chest,liver,node)
```
Bronchoscopy +/- endobronchial US
Thoracoscopy for pleural disease
Surgical
79
Resp disorders and management: What is lung cancer treatment dependent on?
Dependent upon stage and WHO Performance status for NSCLC
80
Resp disorders and management: What is the treatment for lung cancer?
RT or surgery for limited disease WHO PS0-1/2
Chemotherapy (platinum + 3rd generation drug) for extensive disease
Immunotherapy – inhibition of PDL suppression by tumours on T-cells
Oral EGFR mAb for EGFR +ve disease WHO PS 0-3
BSC for patients not fit for active treatment
For SCLC
Systemic Cisplatin based Chemotherapy - disease extensive at presentation
Treat within 7/7 of diagnosis to due speed of deterioration
If localised disease – f/u RT
81
Resp disorders and management: What are the types of interstitial lung disease?
Interstitial Lung Disease
Diffuse Parenchymal Lung Disease
Lung Fibrosis
82
Resp disorders and management: how is interstitial lung disease classfied? - look at this again
Idiopathic
Drug reaction
Extrinsic Allergic Alveolitis/Hypersensitivity Pneumonitis
Associated with rheumatological disease
83
Resp disorders and management: What are the symptoms of interstitial lung disease?
```
Dyspnea
Cough
Constitutional symptoms
Onset of symptoms may identify aetiology
EAA – post exposure
IPF – chronic
AIP – rapid onset
```
84
Resp disorders and management: What are the signs of interstitial lung disease?
Signs associated with CTD/RA
Nail clubbing
Sclerodactyly
Signs of steroid use
Chest – audible crackles; distribution may influence diagnosis
Chest - squeaks - suggest small airways disease
85
Resp disorders and management: What are the features of idiopathic pulmonary fibrosis?
```
Male
Older population
Median survival 3years
Associated with clubbing
Mainly lower zone preponderance
Classically restrictive spirometry and reduced transfer factor
Diagnosis can be made from CT
```
86
Resp disorders and management: What is the treatment for idiopathic pulmonary fibrosis?
```
Treatment
Supportive
Pulm Rehab
Pirfenidone (anti-fibroblast activity with effect on survival & lung function) when FVC<80%
Nintenadib (anti-fibroblast FVC 50-80%)
Opiates/Palliative Care in later stages
Role of steroids controversial
```
87
Resp disorders and management: What is sleep apnea?
Excessive daytime sleepiness with disordered nocturnal irregular breathing
..... SLIDE 82
88
Resp disorders and management: What are the three types of sleep apnea?
Obstructive Sleep Apnea (OSA)
Central Sleep Apnea
Mixed Apnea
89
Resp disorders and management: What other factors can cause OSA?
```
Obesity
>17inch collar
Men x2-3 likely
Age
Cranio-facial & upper airway abnormalities e.g short mandible, tonsillar/adenoid hypertrophy, wide craniofacial base
```
90
Resp disorders and management What is the Epworth sleepiness scale?
Questionnaire with 0-24 scale
11-14 mild sleepiness
15-18 moderate sleepiness
>18 severe sleepiness
Screening tool when assessing daytime somnolence
Other tests
Sleep latency test & Maintenance of Wakefulness
91
Resp disorders and management: Pulse oximetry vs polysomnography
pO
Cheap
Easy to use
Can be used at home
Can show false negative
Less sensitive in thin patients/issues with tissue perfusion
Measure 4% desaturation rate (ODI) - >10 events per hours suspicious
polysomnography
Limited vs Full
Full considered Gold standard
Full PSG requires hospital admission
Measurement of EEG, eye & limb movements, nasal flow, thoraco-abdominal movement, ECG & oxygen saturation
92
Resp disorders and management: When are short acting bronchodilators used?
Short acting relief
```
For PRN use
Use in COPD & Asthma
Immediate bronchodilation
4-6hour duration
Increase in cAMP with reduction in cell Ca2+ leading to relaxation of smooth muscle
```
93
Resp disorders and management: What are the side effects of short acting bronchodilators?
```
Side effects
Increased HR & palpitations
Tremor
Hypokalaemia
Headache
Nervousness
```
94
Resp disorders and management When are long acting bronchodilators used?
Alternative to increasing dose of steroids
Given by inhaled route
Not to be used in monotherapy in Asthma
High selectivity for B2 adenoceptor in pulmonary tissue
Can increase glucocorticord receptor availability
95
Resp disorders and management: What are the side effects of long acting bronchodilators?
Concern of sudden cardiac death when used in monotherapy
96
Resp disorders and management: What are anticholinergic agents used for?
Relief of symptoms
Primarily for COPD
Reduction in exacerbation frequency in COPD
Improvement in FEV1
Mode of action Blockade of muscarinic receptors M1-3
Systemic absorption low
97
Resp disorders and management: What are the side effects of anticholergic agents?
Side effects
Possible effect on urinary retention
Dry mouth
Possible adverse cardiovascular effects (seen in severe cardiac disease)
98
Resp disorders and management: What are inhaled steroids used for and what are the side effects?
Mainstay of asthma medication
Prevent symptoms
Reduces risk of exacerbations and death
Usually twice daily medication
Not useful in acute attack
Binds to cytosolic GR with reduction in cytokines
Reduces bronchoconstriction and airway inflammation
Side effects
Oral candida
Voice change
Risk of skin bruising, bone mineral density change and cataracts with high dose
99
Resp disorders and management: What are oral steroids used for and what are the side effects?
Given in acute asthma or chronically in severe asthma
Avoid if possible as long term therapy but essential if asthma worsens
Clearer role in eosinophilic asthma
Time to efficacy 4hours for IV & PO routes
```
Side effects
Weight gain
Hyperglycaemia
Skin change
Hypertension
Eye change
Mood change
Reduce bone mineral density
```
100
Resp disorders and management: What are theophyllines used for and what are the side effects?
```
Tablets and intravenous
Useful in acute and chronic asthma
Method of action unclear
Possibly acting upon cAMP via PDE inhibition
Possibly acting upon HDAC pathway
Requires serum level monitoring
Drug interactions
```
```
Nausea
Vomiting
Palpitations
Headaches
Dyspepsia
Arrhythmias
Confusion
```
101
Resp disorders and management; What are antileukotrienes used for and what are the side effects?
Oral
Useful in chronic asthma
Not useful in acute asthma
Role in exercise induced asthma & patients with aspirin hypersensitivity
Leukotrienes within phospholipid cell membranes and derived from inflammatory cells
Can promote smooth muscle contraction and inflammatory changes in airway wall
```
Side effects
Headache
N&V
Sleep disturbance
Sore throat
GI disturbace
```
102
Pathology of lung disease: What is the definition of asthma?
```
• increased irritability of the bronchial tree
• paroxysmal airway narrowing
• reversible
– spontaneous
– after treatment
```
103
Pathology of lung disease: What is atopic asthma?
* triggered by environmental agents e.g. dust
* family history of asthma, hay fever etc.
* type I hypersensitivity reaction
104
Pathology of lung disease: What is the mechanism of atopic asthma?
The inflammatory reaction is caused by mast cells in the bronchi. On the surface of these mast cells are IgE antibodies which have been formed by the body to some sort of allergen, usually some component of house dust.
When somebody with asthma inhales the allergen, shown here as a red circle, the allergen binds to the specific IgE antibodies on the surface of the mast cell and cross links those antibodies.
This cross-linking of the antibodies triggers the mast cell to de-granulate. This releases a large number of inflammatory mediators from the mast cell into the surrounding cells in the bronchus causing an acute inflammatory reaction
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Pathology of lung disease: What is chronic bronchitis?
cough and sputum for 3 months in 2 consecutive years
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Pathology of lung disease: What is the cause of chronic bronchitis?
* cigarette smoking
| * air pollution (Clean Air Act 1956)
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Pathology of lung disease: Who is most likely to get chronic bronchitis?
* middle-aged men
| * heavy cigarette smokers
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Pathology of lung disease: What is the pathology of chronic bronchitis?
* mucus hypersecretion
* chronic inflammation
* squamous metaplasia
* dysplasia (but a feature of the causative agent)
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Pathology of lung disease: What is the microbiology of chronic bronchitis?
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• bacteria
– Haemophilus influenzae
– Streptococcus pneumoniae
• viruses
– respiratory syncytial virus
– adenovirus
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Pathology of lung disease: What is emphysema?
* anatomical
* enlargement of airspaces distal to the terminal broncioles with destruction of elastin in walls
losing SA of the lungs - breathless, can't diffuse enough oxygen in
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Pathology of lung disease: What are the causes of lung cancer?
* cigarette smoking 85-90% all cases
* asbestos exposure
* radon exposure
* nickel, chromate etc.
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Pathology of lung disease: What are the cellular changes that occur in lung cancer?
ciliated columnar
metaplasia occurs
squamous
dysplastic
invasive cancer
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Pathology of lung disease: What are the types of lung cancer?
Small cell
non small cell - more treatable surgically
- adeno
- squamous
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Pathology of lung disease: What is the prognosis of lung cancer?
* only 15-20% of lung cancers are resectable at the time of presentation
* all the rest are unresectable due either to locally advanced tumours (e.g. gross involvement of subcarinal lymph nodes) or metastasis
• 4-9% overall 5 year survival rate
– this reflects the low percentage of resectable tumours
– and the poor response to systemic chemotherapy
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Pathology of lung disease: What are the economics of lung cancer?
• probable positive economic balance
– tax from cigarette purchases for 40 years
– develop the disease just before or around retirement age
– die relatively quickly from the disease
– treatment is relatively cheap
• however even in economic terms alone cigarette smoking has an overall debit due to:
– chronic obstructive airways disease
– ischaemic heart disease
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Pathology of lung disease: What is coal worker's pneumoconiosis?
black lung disease or black lung, is caused by long-term exposure to coal dust. It is common in coal miners and others who work with coal. It is similar to both silicosis from inhaling silica dust and asbestos dust.
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Pathology of lung disease: What is silicosis?
Silicosis is a lung disease. It usually happens in jobs where you breathe in dust that contains silica. That's a tiny crystal found in sand, rock, or mineral ores like quartz. Over time, silica can build up in your lungs and breathing passages. This leads to scarring that makes it hard to breathe
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Pathology of lung disease: What are asbestos-related diseases?
* pleural plaques
* pleural fibrosis
* mesothelioma • asbestosis
* lung carcinoma
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Pathology of lung disease: what is mesothelioma?
a type of cancer that develops in the lining that covers the outer surface of some of the body's organs. It's usually linked to asbestos exposure
* almost always associated with asbestos exposure especially crocidolite (Cape blue asbestos)
* malignant tumour of pleura
* long latent period
* incidence will continue to rise into 21st century
