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Flashcards in Session 6 (COPD AND TB) Deck (50):
1

Describe the main causes of Chronic Obstructive Pulmonary Disease

[*]     ~1 million people suffer with COPD in the UK, most presenting between the ages of 50 and 60 in the world.

  • COPD is the leading cause of respiratory disability in the UK among older people
  • The prevalence of COPD is increasing in the developing world in line with increases in tobacco consumption
  • 30,00 deaths per year in the UK as a result of COPD
  • 1 million hospital inpatient days/year
  • COPD is common and a leading cause of morbidity and mortality

[*]     COPD is a chronic disease state characterised by airflow obstruction. The airflow obstruction is usually progressive, not fully reversible and does not change markedly over several months. [NIC]

[*]     Tobacco smoking is responsible for 90% of COPD cases.

  • ~15% of smokers will develop COPD
  • Why not all? Probably determined by genetic factors

[*]     Air pollution and occupational exposure e.g. coal dust are other causes

[*]     Alpha-1 antitrypsin deficiency (inherited) is less common (~1%)

  • Alpha-1 antitrypsin is an antiproteinase; the imbalance in proteinases and antiproteinase leads to destruction of alveolar walls and to emphysema that usually presents at an early age

2

 COPD is an umbrella term encompassing both emphysema and chronic bronchitis. What is emphysema?

In emphysema, the final outcome is elastin breakdown and subsequent loss of alveolar integrity leading to permanent destructive enlargement of the airspaces distal to the terminal bronchioles. Destruction of the terminal bronchioles and distal airspaces leads to loss of the alveolar surface area and therefore the impairment of gas exchange.

  • The process often progresses to the development of larger redundant airspaces within the lung called bullae.
  • Emphysema causes destruction of the supporting tissue surrounding the small airways, which therefore tend to close during expiration when the pressure outside the airways rises. This results in airflow obstruction particularly affecting the small airways.
  • In addition, the loss of elastic tissue in the lung (loss of elastic recoil) causes the lungs to hyperinflate (fill up the thoracic cavity) because the lungs are unable to resist the natural tendency of the rib cage to expand outwards. 

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3

What is chronic bronchitis? Can it occur in COPD at the same time as emphysema?

In chronic bronchitis, another phenotype of COPD, the final outcome is excessive mucus secretion and impaired removal of the secretions (due to ciliary dysfunction). (frequently occurs in smokers)

  • Mucus hypersecretion is caused by inflammation in the large airways leading to proliferation of mucus producing cells in the respiratory epithelium
  • The result is a chronic productive cough and frequent respiratory infections. In COPD, this frequently persists even after smoking has stopped
  • Chronic bronchitis is part of an inflammatory process usually triggered by smoking that results in airflow obstruction due to remodelling and narrowing of the airways (vicious cycle)
  • Usually both emphysema and chronic bronchitis co-exist in patients with COPD. In both conditions, changes are progressive and usually not reversible. Patients may have features of either or both

The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases

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4

How is airflow limitation brought on by the chronic inflammatory response?

[*]     The host response to inhaled cigarette smoke and other noxious substances causes a chronic inflammatory process and oxidative injury, which affects central and peripheral airways, lung parenchyma, alveoli and pulmonary vasculature. The pathological changes in the lung include

  • Enlargement of mucus-secreting glands of the central airways
  • Increased number of goblet cells (which replace ciliated respiratory epithelium)
  • Ciliary dysfunction
  • Breakdown of elastin leading to destruction of alveolar walls and structure, and loss of elastic recoil (lungs more likely to remain hyper-expanded)
  • Formation of larger air spaces with reduction in total surface area available for gas exchange
  • Vascular bed changes leading to pulmonary hypertension

5

How does emphysema and chronic bronchitis lead to airway resistance? And what could persistent hypoxia eventually lead to?

[*]     Emphysema and chronic bronchitis lead to increased airway resistance due to

  • Luminal obstruction of airways by secretions
  • Narrowing of small bronchioles which are usually kept open by the outward pull (radial traction) exerted on their walls by elastin in the surrounding alveoli.
  • Decreased elastic recoil leads to reduced expiratory force, hence air trapping. Expiratory flow limitation promotes hyperinflation.

[*]     Airway narrowing and destruction of lung parenchyma, predisposes COPD patients to hypoxia, particularly during activity.

[*]     Progressive hypoxia causes pulmonary vasoconstriction and vascular smooth muscle thickening with subsequent pulmonary hypertension and right heart failure (Cor pulmonale)

6

Describe the symptoms and signs of COPD

COPD has a gradual onset and usually presents in older people with a long history of smoking. Cough and sputum production are frequently the first symptoms of COPD but many patients do not present until they are breathless

7

Describe the cough in COPD

  • Usually the initial symptom of COPD
  • Frequently a morning cough, but becomes constant as disease progresses
  • Usually productive and sputum quality may change with exacerbations or superimposed infection
  • Sputum may be white or clear but give antibiotics as soon as sputum turns yellow or green

8

Describe SOB in COPD

[*]     Shortness of breath occurs initially on exertion but may progress to shortness of breath even at rest. The MRC Dyspnoea Score grades breathlessness related to activities. It is a useful for measuring progress and the baseline for when looking at exacerbations.

  1. Not troubled by breathlessness except on strenuous exercise
  2. Short of breath when hurrying or walking up a slight hill
  3. Walks slower than contemporaries on level ground because of breathlessness or has to stop for breath when walking at own pace
  4. Stops for breath after walking about 100m or after a few minutes on level ground
  5. Too breathless to leave the house, or breathless when dressing or undressing

9

What are exacerbations?

[*]     Exacerbations (acute flare-ups) are associated with increases in breathlessness (compared to baseline) and increased cough and sputum production. Patient may be infective or non-infective

10

Why do you get the pursed lip sign in COPD?

The “purse lip” breathing often seen in patients with COPD is a protective manoeuvre that increases the pressure within the airways. This causes a reduction or a delay in the closure of these airways

11

Describe the signs in physical examinations indicative of COPD

[*]     Physical examination (more Signs)

  • Tachypnoea: increased respiratory rate to compensate for hypoxia and hypoventilation
  • Use of accessory muscles of respiration due to difficulty in moving air in and out lungs
  • Barrel chest (increased antero-posterior diameter of the chest) is due to hyperinflation and air trapping secondary to incomplete expiration – diaphragm and other respiratory muscles have to work much harder to ventilate the lungs
  • Hyper-responance on percussion due to hyperinflation and air trapping
  • Patients may have wheeze or quite breath sounds on auscultation

- Reduced intensity (distant) breath sounds caused by barrel chest, hyperinflation and air trapping.

- Reduced air entry (poor air movement) secondary to loss of lung elasticity and lung tissue breakdown.

- Wheezing may be present.

Late features include

  • Central cyanosis – hypoxia due to respiratory failure
  • Flapping tremors due to CO2 retention (hypercapnia)
  • Signs of right-sided heart failure (distended neck veins, hepatomegaly and ankle oedema) secondary to pulmonary hypertension

12

Explain about Lung Function Tests used in diagnosis of COPD

  • The measurement of airflow obstruction is necessary for the diagnosis of COPD – achieved with spirometry, a non-invasive and reproducible technique.
  • Spirometry shows an obstructive pattern with FEV1/FVC ratio (<70%)  and FEV1 <80% predicted and limited reversibility following treatment with bronchodilators. Time volume plots (vitalograph) and flow volume loops) show the typical obstructive pattern
  • In COPD there is limitation to the flow of air during expiration and therefore the volume of air expired in the first second (the FEV1 is reduced). This is further compounded by airways collapse on expiration.
  • As well as confirming the diagnosis of COPD, spirometry gives a measure of the severity of airflow obstruction. The NICE guidelines suggest the following:

Mild airflow obstruction: FEV1 (50-80%) predicted
Moderate airflow obstruction FEV1 (30-49%) predicted
Severe airflow obstruction (FEV1 <30%) predicted

  • Decreased diffusing capacity of the lung for carbon monoxide (DLCO – Transfer factor) is a feature of emphysema

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13

Why are Chest X-rays performed when considering COPD?

[*]     Chest X Ray  (not diagnostic but is mandatory to exclude other diagnoses): hyper-inflated lungs may result in

  • A flattened diaphragm
  • Hyperlucent lungs
  • An increased antero-posterior diameter of the chest

May also show complications of COPD such as pneumonia and pneumothorax and is also useful to rule out other pathologies (e.g. lung CA in a patient presenting with chronic cough)

14

Explain about HRCT, pulse oximetry and Alpha1-antitrypsin level testing

[*]     High-resolution computed tomography (HRCT) scanning provides a detailed assessment of the degree of macroscopic alveolar destruction in emphysema. This may be helpful if surgical intervention is contemplated or if the diagnosis is in doubt, but is not required for routine assessment of COPD.

[*]     Pulse oximetry and/or ABG analysis: is carried out in acutely unwell patients to assess for hypoxia and hypercapnia (respiratory failure). ABG is also done to screen for those requiring treatment with home oxygen therapy.

[*]     Alpha-1 antitrypsin level: checked if there is high suspicion such as a positive family history and atypical COPD (young patients and non-smokers). The levels are low in patients with alpha-1 antitrypsin deficiency

15

How would you differentiate between asthma and COPD clinically?

  • Asthma: onset of asthma is in early life. A personal or family history of allergy, rhinitis and eczema is often present. Symptoms may be episodic with obvious triggering factors. There is daily variability in symptoms and patients have over wheezing that rapidly responds to bronchodilators.
  • In asthma lung function test show reversibility with bronchodilators and no decrease in DLCO. Sputum or blood eosinophilia is suggestive of asthma. 

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16

Describe the diagnosis of COPD

The diagnosis of COPD relies on the combination of suggestive symptoms and signs together with the presence of airflow obstruction on spirometry (FEV1 <80% predicted and FEV1/FVC ratio <70%)
The following features are suggestive of COPD:

  • Smoker or ex-smoker
  • Older patient (>40 years old) and onset of symptoms in later life
  • Chronic productive cough
  • Breathlessness that is usually persistent and progressive

17

Describe the management of stable COPD

[*]     Smoking cessation

[*]     Patient education

[*]     Pneumococcal vaccination is strongly recommended in COPD patients (flu vaccine, preventing other complications)

[*]     Patient weight, nutrition status and physical activity should be monitored

[*]    Bronchodilators

[*]     Inhaled corticosteroid – steroids

[*]    Mucolytics
[*]    Antimuscarinics

[*]     Methylxanthines

[*]     Long term oxygen therapy if appropriate

[*]     Lung volume reduction if appropriate (surgical procedure)

[*]     Pulmonary rehabilitation

[*]     Long term Oxygen Treatment: such as removal of large bullae, lung volume reduction and lung transplant are the last step in the management of COPD. They are used to improve lung dynamics, exercise adherence and a quality of life.

[*]     Smoking Cessation, Long term oxygen therapy and lung volume reduction: evidence-based medicine suggests increased survival.

[*]     The other approaches focus on improving quality of life. Drugs can help improve quality of life and reduce exacerbation frequency but do not provide cure or improve survival in COPD.

[*]     Patient education and review regarding adherence and inhaler technique is essential.

18

Why is smoking cessation important in the management of COPD?

Smoking cessation is a key management step in COPD patients to prevent disease progression (and for all smokers to prevent diseases such as respiratory, cardiovascular, cancer, stroke etc)

The single most useful measure in the management of COPD is persuading the patient to stop smoking (if they do). Even in advanced disease, this may slow down the rate of deterioration

19

Describe the action of bronchilators and possible side effects

B2-agonist (e.g. salbutamol) mechanism of action: ligand binds to receptor activity adenyl cyclase, increasing cAMP and activating Protein Kinase (PKA), leading to phosphorylation of downstream targets (myosin light chain kinase – MLCK) leading to relaxation of smooth muscle in airway => bronchodilation


Adverse effects

  • Tachycardia (atrial B2-receptors)
  • Tremor (skeletal B2 receptors)
  • Anxiety
  • Palpitations
  • Hypokalaemia (skeletal muscle uptake K+)

20

Describe the action of steroids and potential adverse effects

[*]     Inhaled corticosteroid – steroids

  • Inhibit antigen presentation, cytokine production and proliferation of lymphocytes – reduce the production of inflammatory chemicals and reduce the activity of the immune system by affecting the function of white blood cells
  • Glucocorticoids bind to glucocorticoid receptors and up-regulates the expression of anti-inflammatory proteins in the nucleus and repressing the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus.
  • Generally, if on less than 800mcg inhaled steroid/ day, unlikely to get significant systemic effects.
  • If above this dose or on oral steroids:

Thin skin
Bruising
Cataracts
Adrenal insufficiency. Patients on long-term steroids must be careful not to suddenly stop taking steroids as over time the HPA axis produces less steroids – gets used to the drugs – so patients might become unwell  due to the adrenal insufficiencies if there is sudden medication cessation.
Osteoporosis
Diabetes
Increased weight (fluid retention)
Mental disturbance
Gi symptoms proximal myopathy

21

What do mucolytics do?

E.g. carbocysteine
Can help to reduce thickness of sputum, helping with airways clearance

22

Describe the action of antimuscarinics and possible side effects

  • Anticholinergics e.g. Ipratropium and Tiotropium
  • Synergistic with B2 agonists (=> bronchodilation)
  • Selectively block the binding of ACh, inhibiting parasympathetic activity ((bronchoconstriction)
  • Greater effect in patients with COPD
  • Adverse effects

Local: dry mouth and cough, sore throat, pharyngitis, URTIs, bitter taste, nausea. Acute glaucoma has been described with nebulized anticholinergics when used in combination with B2-agonists

Systemic: supraventricular tachycardia, atrial fibrillation, urinary difficulty, urinary retention, constipation. Systemic anticholinergic effects are pharmacologically predictable rare. 

23

Describe the action of methyxanthines

[*]     Methylxanthines e.g. Theophylline, aminophylline

Mode of action

  • Bronchodilation
  • Increase respiratory drive
  • Increase strength of respiratory muscles
  • Anti-inflammatory effects

Mechanism of action

  • - Inhibition of phosphodiesterases. Phosphodiesterases break down cAMP so inhibition leads to an increase in cAMP => bronchodilation

Toxicity: tachycardia / supraventricular tachycardia, nausea, seizures – need regular blood level monitoring

24

Describe what is meant by Long Term Oxygen Therapy

[*]     Long term oxygen therapy if appropriate

  • Extended periods of hypoxia cause renal and cardiac damage – can be prevented by LTOT
  • Continuous oxygen therapy for most of the day – at least 16 hours/day for a survival benefit
  • LTOT offered if pO2 consistently below 7.3 kPa (when patients are well) or below 8kPA with cor pulmonale.
  • Patients should be non-smokers and not retain high levels of CO2 (smoking is also a fire hazard near oxygen cylinders)
  • O2 needs should be balanced with loss of independence and reduced activity which may occur. 

25

What is meant by Lung Volume Reduction?

Lung volume reduction – the reduction of hyperinflation is the principal aim of surgical techniques in the treatment of appropriately selected COPD patients.

Lung transplant may be an option for young patients    

[*]     Long term Oxygen Treatment: such as removal of large bullae, lung volume reduction and lung transplant are the last step in the management of COPD. They are used to improve lung dynamics, exercise adherence and a quality of life. 

26

What is meant by Pulmonary Rehabilitation

[*]     Pulmonary rehabilitation: many COPD patients avoid exercise because of breathlessness. This leads to muscle weakness and leads to a vicious cycle of worsening symptoms including decreased appetite, social isolation and depression (deconditioning).

Pulmonary rehabilitation aims to break this cycle with a MDT (multi-disciplinary team) programme of supervised exercise, unsupervised home exercise, peer support disease education and nutritional advice. 

27

What does Multidisiciplinary Management mean?

[*]     Multidisciplinary Management: Aim to improve quality of life. Team includes physicians, GPs, specialist nurses, physiotherapists, pharmacists, occupational therapists, dieticians and sometimes surgeons

[*]     Stable COPD is managed by an experienced MDT delivered as a “care bundle” with non-pharmacological interventions as well as drugs, all aimed at improving quality of life. 

28

What are Acute Exacerbations of COPD and describe management

[*]     Acute exacerbation of COPD is defined as an event characterised by a change in the patient’s baseline dysponea, cough and/or sputum that is beyond normal day-to-day variations and is acute in onset.

Acute infectious exacerbations present with acute, severe shortness of breath, fever and chest pain


Management includes:

  • Monitoring for hypoxia and hypercapnia, using Pulse oximetry and ABG analysis
  • Appropriate antibiotics particularly to cover Haemophillus influenza and Streptococcus pneumonia is very important – can be indicated by raised CRP/WCC or purulent sputum
  • Consider IV aminophylline
  • Nebulised bronchodilators
  • Oral steroids (a short course of high dose oral prednisolone), sometimes IV
  • 24% or 28% Oxygen therapy while keeping under review for CO2 retention. Aim for Sats 88-92%
  • Consider non-invasive ventilation for worsening Type 2 respiratory failure (if repeat ABG is not better) or even ITU referral for invasive ventilation

29

Describe Non-invasive Ventilation and what are contraindications to NIV?

Non Invasive Ventilation/BIPAP: the provision of ventilator support through the patient’s upper airway using a mask or similar device

  • Useful for acute exacerbations of COPD with Type II Respiratory Failure and mild acidosis (pH 7.25 – 7.35). Optimises gas exchange by
  • Patients must be conscious to use it
  • Prevents patients requiring intubation and ITU support

Contraindications to NIV/BIPAP:

  • Untreated pneumothorax
  • Impaired conscious level (usually GCS <8)
  • Upper airway secretions
  • Facial injury
  • Life threatening hypoxia
  • Vomiting
  • Agitated

30

What are complications of COPD?

  • Recurrent pneumonia
  • Pneumothorax: occurs because of lung parenchyma damage with sub-pleural bulla formation and rupture
  • Respiratory failure
  • Cor pulmonale (right heart failure)

31

Describe the microbiology of mycobacterium tuberculosis

[*]     Globally approximately ~2 billion people are infected.

[*]     Tb is a chronic communicable disease caused by Mycobacterium Tuberculosis

[*]     TB bacilli are aerobic, acid and alcohol fast bacilli.

[*]     They can demonstrated on smears (e.g. sputum smears) stained by Ziehl-Nielsen method and grow slowly on culture (on media such as the Lowenstein-Jensen Medium) taking 2-6 weeks to form colonies.

  • Mycobacteria possess a lipid-rich cell wall that retains some dyes, even resisting decolourisation with acid (acid-fast)

32

Describe the transmission of TB

[*]     TB is transmitted from person to person by aerolized droplets.

  • The unit of infection is a small particle called a droplet nucleus.
  • Coughing, sneezing, talking and other respiratory manoeuvres by infective individuals will produce small respiratory droplets which undergo evaporation to form droplet nuclei
  • These disperse in the air without settling, and the organisms they contain remain viable for extended periods of time
  • Outdoors, the organisms in droplet nuclei are eventually eliminated by infinite dilution and by radiation from the sun

[*]     The infectivity of sputum becomes minimal after 2 weeks of commencing treatment with effective anti-TB chemotherapy. However treatment must continue for the full duration (e.g. six months of pulmonary TB) to eradicate disease in the infected person.

33

Describe the pathology of TB

[*]     Alveolar macrophages phagocytose MTB deposited in alveoli but are unable to kill them (the cell wall lipids of MTB apparently block fusion of the phagosomes and lysosomes)

[*]     These macrophages initate the development of cell-mediated immunity which eventually leads to the emergence of activated macrophages with enhanced ability to kill MTB. This takes about six weeks to develop.

[*]     Ingestion of MTB by macrophages causes a granulomatous reaction. The characteristic lesion of tuberculosis is a spherical granuloma with central caseation (also known as tubercles)

[*]     Microscopically a TB granuloma consists of necrotic cheese like core (caseous necrosis) surrounded by epitheloid macrophages, Langerhans giant cells and lymphocytes (REVISE MOD)

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34

What is primary TB?

[*]     The Primary Infection occurs on first exposure.

  • The deposition of TB bacilli in the alveoli is followed usually by development of sub-pleural focus of tubercles called the Primary Focus or Ghon’s Focus. This may be in any lung zone.
  • TB bacilli drain from the primary focus into the hilar lymph nodes.
  • The primary (Ghon’s) focus + the draining lymph nodes together are called the Primary Complex

[*]     Most primary infections will heal with or without calcification of the primary complex. However in the majority of subjects, before healing occurs, some TB  bacilli enter the bloodstream (probably via lymph drainage to the venous system) and haematogenous spread occurs resulting in the seeding of tubercle bacilli to other parts of the lung as well as other organs (extrapulmonary sites)

35

Explain about latent TB

[*]     With the development of cell-mediated immunity the infection is contained. The primary complex heals but a small number of organisms remain viable in the lungs/other organs. This state, where TB bacilli can persist within the human host, without causing disease, for years or until death due to other causes, is known as latent tuberculosis.

  • The patient remains well but the potential for reactivation at any site is always present.
  • Reactivation usually occurs when the patient’s immune mechanisms wane or fail (e.g. old age, malnutrition, HIV, immunosuppression)
  • Latent TB is characterised by a positive tuberculin skin test (or positive ‘Quantiferon’ test). The skin test is based on demonstrating a type IV hypersensitivity reaction to proteins derived from Mycobacteria. In the naturally infected host, immunity and hypersensitivity usually develops simultaneously.

36

Differentiate between Primary and Post-Primary TB infections

[*]     Primary TB: the primary complex does not heal but continues to progress and causes disease which is known as Primary Tuberculosis. The pathological changes in primary TB are similar to those seen in reactivation TB. Most infections resolve with local scarring.

[*]     Post Primary TB: the vast majority of clinical cases of TB are due to reactivation of latent TB and occurs most often in the lungs. Post primary TB can also be due to reinfection. Post-Primary Infection refers to the development of tuberculosis beyond the first few weeks. The infection may progress throughout the body (Miliary Spread). This may resolve spontaneously or develop into localised infection (e.g. meningitis).

37

Explain about Post-Primary Pulmonary TB

[*]     Post Primary Pulmonary TB: most often seen in the upper lung zones. The high ventilation/perfusion ratio with higher alveolar pO2 in upper zones of the lungs relative to the other parts of the lung is believed to predispose to reactivation of TB bacilli at these sites. This can lead to the following occurring:

  • Proliferation of TB bacilli in the caseous centres is followed by softening and liquefaction of the caseous material which may discharge into a bronchus resulting in cavity formation. The intense immune system causes local tissue destruction (cavitation I nthe lung) and cytokine-mediated systemic effects (fever and weight loss)
  • Fibrous tissue forms around the periphery of such tuberculous lesions but is usually incapable of limiting extension of the tuberculous process
  • Haemorrhage resulting from extension of the caseous process into vessels in the cavity walls => haemoptysis (coughing up blood)
  • Spreading of caseous and liquefied material through the bronchial tree may disseminate the infection to other lung zones with or without the development of a vigorous inflammatory exudate.

- A marked inflammatory exudate filling the alveoli causes consolidation and is known as tuberculosis pneumonia (i.e. clinically and radiologically it may appear similar to a bacterial pneumonia, but the causative organism is mycobacterium tuberculosis)

  • Seeding of TB bacilli in the pleura or hypersensitivity can result in a pleural effusion.

38

How can TB affect other organs?

[*]     Rupture of a caseous pulmonary focus into a blood vessel may result in military tuberculosis with the formation of multiple ‘miliary’ (millet seed like) 0.5-2mm tuberculous foci in the lung and in other organs of the body.

[*]     TB may affect every organ of the body, mimicking both inflammatory and malignant diseases.

  • Pulmonary TB may present with a chronic cough, haemoptysis, fever and weight loss or as recurrent bacterial pneumonia. Untreated, the infection follows a chronic deteriorating course
  • Tuberculosis meningitis presents with fever and slowly deteriorating level of consciousness
  • Kidney infection may lead to signs of local infection, fever and weight loss, complicated by ureteric fibrosis and hydronephropathy
  • The lumbosacral spine is a common site of bone infection – progression may cause vertebral collapse and nerve compression
  • Inflammation of large joints may lead to destructive arthritis

39

Describe the host response to TB infection

[*]     MTB is ingested by macrophages but escapes from the phagolysosome to multiply in the cytoplasm

[*]     At the same time it provokes an immune response, stimulating the release of Interleukin-12.

[*]     IL-12 in turn drives the release of IFN-gamma and TNF-alpha from Natural Killer and CD4 cells. These cytokines activate and recruit more macrophages to the site of infection, resulting in the formation of Granulomas.

[*]     Clinical Disease: those infected with TB have about a 10% life time risk of developing active disease.

5% develop primary TB at the time of the initial infection
Another 5% develop post primary TB due to reactivation of latent TB after a variable period of time (up to 60 years) following the primary infection

40

Describe the primary and post primary changes in TB

[*]     Primary changes:

  • Few symptoms
  • Lymph nodes may become enlarged in young people

[*]     Post-Primary changes

The classical presentation:

  • Cough (not always productive)
  • Fevers towards the end of the day or at night
  • Weight loss and general debility

[*]     The chest x-ray reveals pulmonary shadowing, which may be patchy solid lesions, cavitated solid lesions, streaky fibrosis or flecks of calcification.

41

Describe the typical clinical presentation and radiographic changes in Respiratory TB

[*]     Signs: Non-specific

  • Pallor
  • Fever
  • Weight loss
  • Clubbing
  • Palpable lymph nodes

[*]     Symptoms:

  • Primary usually asymptomatic
  • Post-Primary: tiredness and malaise, weight loss and anorexia, fever, cough, breathlessness

[*]     X-Ray Changes

  • Shadowing
  • Cavities
  • Consolidation
  • Calcification
  • Cardiomegaly
  • Miliary seeds

42

Describe the typical clinical presentation and radiographic changes in Non-Respiratory TB (including lymph node TB, orthopaedic TB, meningitis, other sites)

[*]     Pleural tuberculosis: more common in males, there are two mechanisms of pleural involvement. There is almost always some pulmonary disease present:

  • Hypersensitivity response in primary infection
  • Tuberculous emphysema with ruptured cavity (has a tendency to burrow through the chest wall)

[*]     Lymph Node tuberculosis: more common in children, women and Asians. It is often painless and occurs most commonly in the neck.

[*]     Oesto-articular TB: TB burrows into bone

Tuberculous Spondylitis

  • Most common form of osteoarticular TB
  • Starts in sub-chondral bone and spread to vertebral bodies and joint space before following the longitudinal ligaments, anterior and posterior to the spine
  • Mainly occurs in the lower thoracic and lumbar spine but can be very high (cervical tuberculosis
  • Paraplegia and quadriplegia occurs in 25% of cases

Poncet’s Disease

  • Aseptic polyarthritis
  • Knees, ankles and elbows

[*]     Miliary Tuberculosis:

  • Bacilli spreading through the bloodstream
  • Either during primary infection or as reactivation
  • Lungs are always involved – evenly spread throughout both lung as it is in the blood, many military seeds are visible through the lungs on an X-ray

Headaches suggest meningeal involvement

  • few respiratory symtpoms
  • Ascites may be present
  • Retinal involvement in children

43

Describe the diagnosis of TB

[*]     TB is diagnosed by clinical and radiological features plus the identification of the tubercle bacillus in the appropriate body fluid by direct smear and subsequently culture.

Cough, night fever, weight loss
Radiological features: shadowing, cavities, consolidation, cardiomegaly, military seeds

[*]     It is very important to isolate the organism and determine its susceptibility to drugs. 

44

Describe the principals of management of TB (including drugs, toxicity, schedules and problems with compliance)

[*]     TB is treatable by a combination of antibiotics. The drugs used include rifampicin, isoniazid, pyrazinamide, ethambutal and streptomycin. A prolonged follow up is needed. TB is a notifiable disease and its diagnosis has public health implications.

[*]     Initially patients are treated with four drugs for 2 months (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol), after which 2 of them are dropped and the others (Rifampicin, Isoniazid) are continued for another four months

[*]     Multiple drugs are used in an attempt to combat resistance (e.g. in 5-10% of patients, TB is resistant to isoniazid)

[*]     As this is quite a long drug regime, with several different pills to take, there can be problems with compliance. As such 15% of patients in the US receive Directly Observed Therapy (DOT), giving benefits including improved cure rates, reduction of rate of drug resistance and relapses.

[*]     Drug reactions

  • Rifampicin: hepatitis, rash, flu-like symptoms, shock, ARF (acute renal failure), thrombocytopenic purpura
  • Isoniazid: rash, peripheral neuropathy, hepatitis
  • Pyrazinamide: rash, hepatitis, arthralgia
  • Ethambutol: otpic neuritis

45

Describe the mechanisms of drug resistance in TB (molecular mechanisms and causes)

[*]     There is a rising trend of Multidrug-Resistant TB (MDRTB). About one in a million bacilli are spontaneously resistant.

[*]     A case of MDRTB is suggested by a history of previous incomplete treatment, residence in a country with high incidence of MDRTB or failure to respond clinically to an adequate regimen.

[*]     A regimen of several drugs at once is used in an attempt to combat resistance.

46

Describe the role of BCG vaccination

[*]     BCG vaccine: vaccination against tuberculosis that is prepared from a strain of the Attentuated Live Bovine Tuberculosis Bacillus. The bacteria retain a strong enough antigenicity to act as a vaccine for human tuberculosis

[*]     Issues: the vaccine has a variable efficacy, depending on genetic variation of populations and BCG strains. Efficacy only lasts 15 years at most.

[*]     UK Regulations: in the UK up until 2005 all children ages 13 were immunised along with all neonates born into high-risk groups. Post-2005 the vaccination were only given to high-risk groups, as falling incidence of TB had reduced the vaccine’s cost effectiveness. 

47

List groups at high risk of TB in the UK

[*]     HIV

[*]     Silicosis (incurable lung disease – caused by inhalation of large amounts of silicon dioxide usually over a period of many years)

[*]    Malnutrition

[*]     Overcrowding - prisons, homeless shelters

[*]     IV drug abusers

[*]     Chronic lung disease (smokers)

[*]     Ethnicity – Asians more likely

[*]    Diabetes

[*]     Corticosteroids/anti alpha-TNF antibody (Infliximab)

48

Describe the relationship between TB and HIV infections

[*]     HIV is a major risk factor for tuberculosis

[*]     The risk of developing TB is estimated to be between 20-37 times greater in HIV infected people than in uninfected people

[*]     TB is a leading cause of morbidity and mortality among HIV patients

49

Describe in broad terms the public health issues surrounding a case of TB (including details of notification)

[*]     If TB is suspected, contact is immediately made with TB radiology. The patient goes straight into a TB clinic with no waiting times, and is given a questionnaire and sputum samples are taken.

[*]     Treatment begins within 7 days.

50

What should I do next?

LOOK OVER THE TB LECTURE!!!