CASE 3 - TB / PNEUMONIA Flashcards

1
Q

List 2 benign and 3 serious differentials for a cough with haemoptysis

A

BENIGN:

  • Acute viral or bacterial bronchitis
  • COPD exacerbation

SERIOUS:

  • Pneumonia
  • TB
  • Lung cancer
  • Pulmonary embolism
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2
Q

List 1 benign and 2 serious differentials for a cough with fever and purulent sputum production

A

BENIGN:
- Acute sinusitis

SERIOUS:

  • Pneumonia
  • Lung abscess
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3
Q

Name the organism that most commonly causes tuberculosis

A

Mycobacterium tuberculosis

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4
Q

How is TB spread?

A

Most commonly, it is person-to-person spread (e.g. coughing, then another person inhales)

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5
Q

How does TB escape hydrolytic enzymes once it has been phagocytosed by the macrophage?

A

TB produces proteins that inhibit the fusion of phagosomes (containing the TB) and lysosomes

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6
Q

Why does TB tend to infect upper lobes first?

A

TB is a strict aerobe (needs oxygen to survive)

The upper lobes have a higher V/Q ratio, less blood (and therefore less WBCs), and more lymphatics

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7
Q

What is the difference between latent and active TB?

A

LATENT: A state of constant immune response stimulation due to M. tuberculosis antigens, with no signs of active TB. ASYMPTOMATIC, NOT CONTAGIOUS.

ACTIVE: Active TB
A disease occurring after first-time exposure to M. tuberculosis (only in 1–5% of cases). SYMPTOMATIC, CONTAGIOUS.

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8
Q

In which population group (in Australia) should TB be considered?

A

MIGRANTS

Indigenous Australians

Elderly Australians (becoming immunocompromised)

Other disadvantaged groups (e.g. prisoners, homeless)

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9
Q

Which types of samples are best for diagnosing TB? Why?

A

Tissue samples (e.g. pleural or peritoneal biopsy)

Mycobacteria have a lipid-rich cell wall. They don’t swim into the aqueous solution: they like to stay cell-associated.

Fluids are low-quality specimens

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10
Q

What type of staining is used to detect TB? Why is a Gram stain not used?

A

Ziehl-Neelsen stain

Mycobacterium tuberculosis has a very lipid-rich cell wall that is not suited to Gram staining

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11
Q

How does a tuberculin skin test / purified protein derivative (PPD) test work?

A

TUBERCULIN (a component of TB) is injected into the skin.

If someone has been exposed to TB before, the immune response causes an area of induration (hardening). If it is large enough, the test is considered POSITIVE.

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12
Q

Highlight the advantages and disadvantages of the tuberculin skin test vs. IGRA

A

TUBERCULIN:
Advantages = inexpensive, a century of experience, preferred in children
Disadvantages = not diagnostic, can’t differentiate between active and latent, requires 2 office visits, variation in interpretation, false positives in BCG vaccination

IGRA (Interferon-gamma release assay)
Advantages = single blood test, specific
Disadvantages = cannot be used for diagnosis, can’t differentiate between active and latent, not as much experience (only been around for around 10 years)

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13
Q

List 2 initial investigations for suspected pulmonary tuberculosis

A

Sputum smear microscopy with Ziehl-Neelsen stain

CXR

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14
Q

What are sputum culture and susceptibility testing used for?

A

Diagnosis & checking for drug resistance

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15
Q

How can sputum samples be obtained for diagnostic purposes?

A

3 early morning sputum samples

Induced sputum

Gastric lavage

Bronchoalveolar lavage

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16
Q

Clinical features of active TB

A

Fever
Weight loss
Night sweats
Productive cough (+/- haemoptysis)

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17
Q

3 most common causes of community-acquired pneumonia

A

Streptococcus pneumoniae (most common)

Haemophilus influenzae
Moraxella catarrhalis

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18
Q

2 most common causes of hospital-acquired pneumonia

A

Gram-negative pathogens (e.g. pseudomonas aeruginosa)

Staphylococcus aureus

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19
Q

Host factors that predispose to pneumonia?

HALM

A

Hypoventilation (e.g. drugs, immobility, pain)

Accumulation of secretions (e.g. COPD, CF, bronchial obstruction)

Loss or suppression of cough reflex (e.g. coma)

Mucociliary impairment (e.g. smoking, viral URTI)

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20
Q

Why does hospital-acquired pneumonia tend to be more dangerous?

A
  • Occurs in immunocompromised individuals

- Hospital pathogens are resistant to more antibiotics and therefore harder to treat

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21
Q

Pneumonia can be categorised according to location. Name and describe the 3 types of pneumonia under this category.

A

LOBAR (typical): consolidation of a whole lung, filling the entire region with fluid

BRONCHOPNEUMONIA: throughout the lungs, involving both bronchioles and alveoli

ATYPICAL/INTERSTITIAL: outside alveoli, in the interstitium

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22
Q

Name 2 other categories of pneumonia

A

Ventilator-associated (a subset of hospital-acquired)

Aspiration

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23
Q

Describe the 4 stages of lobar pneumonia and their timeline

A
  1. CONSOLIDATION (1-2 days): blood vessels and alveoli fill with excess fluid
  2. RED HEPATIZATION (days 3 - 4): exudates such as RBCs, neutrophils, and fibrin fill airspaces, making them more solid. Named for its liver-like appearance.
  3. GREY HEPATIZATION (days 5 - 7): still firm, but colour change is due to the breakdown of exudates
  4. RESOLUTION (day 8 - 3 weeks): exudate is digested (by enzymes) or coughed up
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24
Q

Name 2 organisms that cause atypical pneumonia

A

Mycoplasma pneumoniae

Chlamydia pneumoniae

(atypical pneumonia usually affects immunocompromised individuals)

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25
Why does atypical pneumonia cause a DRY cough?
Because consolidation/fluid buildup occurs in the interstitium and not the alveoli
26
Describe 4 symptoms of someone who has TYPICAL pneumonia.
CONSTITUTIONAL SYMPTOMS: Severe malaise, high fever, chills - Productive cough w/purulent sputum production - Pleuritic chest pain - SOB (CPPS)
27
Describe 4 SIGNS of someone who has TYPICAL pneumonia.
- Dullness on percussion (e.g. in lobar pneumonia where there is consolidation) - Late inspiratory crackles and bronchial breath sounds (heard in the sternal and upper back region, between the scapula - where the large bronchi are located) on auscultation - Increased vocal resonance over areas of consolidation (sound travels better through fluid) - Tachypnoea, dyspnoea
28
How is pneumonia diagnosed?
It is a clinical diagnosis based on: - HISTORY - PE - Lab findings - CXR findings
29
Describe what can be seen on the CXR of someone with pneumonia.
LOOK UP IMAGE LOBAR: opacity of one or more lobes, air bronchograms (refers to the phenomenon of air-filled bronchi (dark) being made visible by the opacification of surrounding alveoli (grey/white)) BRONCHOPNEUMONIA: poorly-defined patchy infiltrates scattered through the lungs, air bronchograms ATYPICAL / INTERSTITIAL: diffuse reticular (linear) opacity, absent (or minimal) consolidation
30
Typical lab findings in pneumonia (CBC, inflammatory markers, ABG)
CBC: leukocytosis Raised CRP & ESR ABG: Decreased PaO2
31
What is primary tuberculosis?
A form of TB that occurs soon after initial infection with mycobacterium tuberculosis (previously unexposed and unsensitised patients). Includes active and latent TB. Patients with primary TB are usually asymptomatic.
32
About 3 weeks after initial tuberculosis infection, cell-mediated immunity kicks in. How does this affect the lungs?
1. GRANULOMA formation: an attempt to wall off the bacteria. 2. CASEOUS NECROSIS: cheese-like necrosis. Granulomas with central caseating necrosis is the hallmark of TB in immunocompetent individuals. 3. GHON FOCUS: granulomas + caseous necrosis AND lymph node involvement
33
What is secondary tuberculosis?
Reactivation of disease in a previously-sensitised host. Often due to a weakened immune response (e.g. HIV, TNF-alpha inhibitor therapy)
34
What is the most frequently occurring case of extrapulmonary TB? Where does it usually occur?
Lymphadenitis - in the cervical region.
35
TRUE OR FALSE? HIV-positive patients almost always have multifocal disease, systemic symptoms, and either pulmonary or other organ involvement by active tuberculosis.
TRUE
36
What is the appearance of TB under microscopy after ZN staining?
Pink rods (look up image) Note: ZN staining does not differentiate between M. tuberculosis and other acid-fast bacilli
37
Outline the investigations used for a suspected case of pulmonary tuberculosis
INITIAL: CXR and sputum microscopy w/acid-fast staining (Ziehl-Neelsen) CONFIRMATION OF DIAGNOSIS AND CHECKING FOR RESISTANCE: sputum culture (gold standard) and susceptibility testing Rapid molecular testing (eg PCR) for rifampicin resistance is recommended if there is a risk of multidrug-resistant TB (MDR-TB)
38
Outline the phases of treatment for TB
First-line INTENSIVE PHASE: 2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol CONTINUATION PHASE: 4 months of rifampicin + isoniazid
39
4 symptoms in someone with pulmonary tuberculosis
CONSTITUTIONAL: weight loss, malaise, low-grade fever, night sweats, anorexia PULMONARY: cough, haemoptysis, pleuritic chest pain, SOB
40
Describe the appearance of bronchopneumonia on CXR
Poorly-defined patchy infiltrates scattered throughout the lungs Air bronchograms
41
How is miliary TB spread?
Haematogenous
42
What causes granuloma formation?
Aggregated macrophages and scattered lymphocytes
43
What is the purpose of granuloma formation in TB infection?
To 'wall off' the offending agent (but doesn't necessarily kill it)
44
Describe differences in the histology between primary and secondary tuberculosis
PRIMARY TUBERCULOSIS tends to have more lymph node involvement SECONDARY TUBERCULOSIS more readily forms cavitations (due to memory T cells)
45
When cavitation is present, the sputum contains ______ _________.
When cavitation is present, the sputum contains TUBERCULE BACILLI.
46
What causes pleuritic pain in tuberculosis?
Extension of the infection to pleural surfaces
47
List 4 physical exam findings in someone with TB
(note: usually nonspecific) GENERAL: pallor, wasting, clubbing CHEST EXAMINATION: - Dullness over areas of consolidation - Hyperresonance over areas of cavitation AUSCULTATION: - Amphoric breath sounds over cavitation - Rhonchi - Crackles - Diminished breath sounds over areas of consolidation (pleural effusion)
48
How does miliary pulmonary disease develop?
1. Organisms drain into lymphatic ducts 2. Venous return to right heart 3. Pulmonary arteries 4. Lesions scattered throughout lung parenchyma
49
What is a complication of miliary pulmonary disease?
Pleural effusion
50
Briefly describe the natural history of primary tuberculosis
90% of individuals with intact immune systems control further bacilli replication, and TB enters a latent phase 10% of individuals develop progressive primary disease. Progression typically occurs in those who are immunodeficient (e.g. HIV, poorly-controlled DM, immunosuppressive therapies, etc.)
51
Approximately 5-15% of people will suffer from reactivation of latent TB. List 3 risk factors for reactivation.
- HIV - Organ transplantation - Kidney dialysis
52
What is the BCG vaccine, and what are its indications for use?
A vaccine primarily used against tuberculosis. 1. Newborns in countries with a high TB burden 2. Countries with a low TB burden: healthcare workers continually exposed to individuals with drug-resistant TB, children exposed to adults w/TB and who are unable to take long-term medication for infection
53
What is the treatment for active TB infection?
Standard short-course therapy: rifampicin, isoniazide, pyrazinamide, ethambutol (RIPE) for 2 months (the intensive phase) Further 4 months of rifampicin and isoniazid (the continuation phase)
54
What susceptibility testing is undertaken for TB?
Gene-Xpert assay Can identify possibly drug-resistant TB. Resistance to rifampicin predicts resistance to other TB drugs because isoniazid resistance often co-exists with RIF resistance.
55
What are the benefits of using the Gene-Xpert assay
Rapid diagnosis of RIF-resistant TB allows patients to start on effective treatment without having to wait for other drug susceptibility testing
56
List the 4 steps that must be undertaken before discharging a TB patient
1. COUGH STATUS: present or absent? This is associated with marked reduced infectiousness. 2. CLINICAL IMPROVEMENT: sputum smears are negative or trend downward 3. TREATMENT ENSURED: directly observed therapy planned 4. HOUSEHOLD SITUATION assessed and public health information given: e.g. wait 2-4 weeks before returning to work
57
Why is supervised treatment recommended?
Missing doses = ineffective treatment. Can also contribute to resistance
58
Why does TB treatment take such a long time?
The bacteria are slow-growing
59
List the side effects of each TB antibiotic
RIFAMPICIN: red bodily fluids, thrombocytopenia ISONIAZID: peripheral neuropathy PYRAZINAMIDE: hyperuricaemia ETHAMBUTOL: optic neuritis, colour blindness Hepatitis: RIP
60
How do rifampicin and isoniazid affect cytochrome P450 enzymes?
RIFAMPICIN: enzyme induction ISONIAZID: enzyme inhibition. Inhibits clearance of other CYP450 drugs, and can result in toxicity. Drugs with a narrow therapeutic index (e.g. warfarin) need to be used with caution (or monitored) in conjunction with isoniazid.
61
Give 5 examples of drugs with narrow therapeutic indices
``` Anti-epileptics Warfarin Methotrexate Aminoglycosides Digoxin ```
62
Why is acid-fast/Ziehl-Neelsen staining used to detect TB?
M. tuberculosis is not easily stained by basic staining such as Gram staining due to the high lipid content
63
How does HIV change the TB treatment regime?
Use the daily regimen for the entire treatment course in HIV-infected patients
64
Why does TB take so long to culture?
It grows slowly Can take 2-6 weeks for blood or sputum culture
65
Why are all 4 antibiotics needed to treat TB?
Prevents resistance Targets M.tuberculosis at different stages of growth
66
Why is pyridoxine used in conjunction with RIPE?
B6 - counteracts the peripheral neuropathy caused by isoniazid.
67
When do cavitating lesions occur? Why is this bad?
Cavitating lesions form after prior sensitisation (secondary TB), causing a stronger immune response Cavitation is bad because it allows TB to disseminate to other parts of the body (miliary TB - haematogenous spread)
68
What is the drug regime for latent TB?
Isoniazid for 9 months
69
PCR can be used to rapidly diagnose TB infection and test for drug resistance/susceptibility. What are some limitations to its use?
Expensive Cannot be used in resource-limited settings LOOK @ AMBOSS TB TABLE ON DIAGNOSIS
70
Outline the empirical antibiotic regime for community-acquired pneumonia (CAP)
Empirical therapy depends on pneumonia severity: 1. Low-severity: monotherapy w/amoxicillin OR doxycycline/clarithromycin for atypical presentations. 2. Moderate-severity: combination therapy w/ benzylpenicillin PLUS doxycycline OR clarithromycin 3. High-severity: Ceftriaxone PLUS cefotaxime OR azithromycin
71
List 3 red flags for hospital admission in adults with CAP
- Tachypnoea (RR>22) - Tachycardia (HR>100bpm) - Hypotension (systolic <90mmHg) - Acute onset confusion - Multilobar involvement - Spo2 <92% on RA - Blood lactate >2mmol/L
72
Name 3 risk factors for pneumonia
Cigarette smoking & alcohol consumption (alters host defences) Older age (>65 years) Predisposing conditions (e.g. COPD, CF, bronchiectasis, lung cancer) Immunocompromised (e.g. DM, HIV) Lifestyle (homelessness, overcrowding, opiods, smokingn, alcohol)
73
A patient states that they have had an allergic reaction to penicillin. What should you ask this patient regarding their allergy?
What type of reaction did she have? (figure out if it’s an adverse effect, e.g. nausea, or an actual allergic reaction, e.g. hives, throat swelling) When did the reaction occur? (how long after receiving the penicillin) How long ago did she have the reaction? (The allergy can resolve if a long time has passed since the exposure) Whether she has tolerated similar medications (i.e. cephalosporins) since the reaction GOOD GUIDE ON UPTODATE
74
Which cell type is responsible for the formation of granulomas and caseous necrosis? Which cytokine promotes its differentiation?
T-helper 1 cells Differentiation from T-helper to TH1 initiated by IL-12
75
Why is mycobacterium tuberculosis considered an "acid-fast bacillus"?
Mycobacteria have a unique waxy cell wall composed of unusual glycolipids and lipids including mycolic acid, which makes them acid-fast, meaning they will retain stains even on treatment with a mixture of acid and alcohol. The mycolic acid coating on mycobacteria repels the haematoxylin dye, but absorbs the eosin dye, giving the characteristic red appearance.
76
What does INCREASED vocal resonance indicate?
Increased tissue density (e.g. consolidation, tumour, lobar collapse).
77
What does DECREASED vocal resonance indicate?
Presence of fluid or air outside of the lung (e.g. pleural effusion, pneumothorax).
78
What does a hyper-resonant percussion note indicate? What is it caused by?
Excess air in the lungs / hyper-inflated lungs. Indicates DECREASED tissue density. E.g. COPD, pneumothorax, emphysema
79
What does a dulled percussion note indicate? What is it caused by?
Increased tissue density E.g. Consolidation, tumour, lobar collapse
80
What does a 'stony' dull percussion note indicate?
Percussing over a fluid-filled structure produces stony dullness. E.g. pleural effusion
81
State the type of percussion note produced by the following: - Solid structures (e.g. liver, collapsed lung) - Normal lung - Hollow structures (e.g. bowel, pneumothorax) - Fluid-filled areas (e.g. pleural effusion)
SOLID STRUCTURES: dull percussion note NORMAL LUNG: resonant percussion note HOLLOW STURCTURES: hyper-resonant percussion note FLUID-FILLED: stony dull percussion note
82
How is tuberculosis diagnosed in patients with symptoms suggestive of active TB?
1. Sputum microscopy, sensitivity, and culture (MC&S). 3 early-morning sputum samples. ``` Microscopy = ZN staining Culture = growing the sample (some cultures can also enable sensitivity to be tested) Sensitivity = cultured isolated tested against TB drugs to detect multi-drug resistant (MDR) cases ``` 2. CXR
83
What are the two types of adventitial (added) breath sounds?
Continuous (wheezes) Interrupted (crepitations)
84
Wheezes tend to be louder on expiration. Why is this? What does an INSPIRATORY wheeze indicate?
Wheezes are louder on expiration because the airway is narrower (airways dilate during inspiration). An inspiratory wheeze indicates severe airway narrowing.
85
What are 2 differences between wheezes and stridor?
Stridor ONLY OCCURS DURING INSPIRATION, whereas wheezing can occur during inspiration and expiration. Stridor is also better heard over the trachea.
86
Crackles in normal people will clear upon _________.
Crackles in normal people will clear upon coughing.
87
Describe the pathophysiology behind: (a) Early inspiratory crackles and (b) Late or pan-inspiratory crackles
(a) Early inspiratory crackles: disease of the small airways, characteristic finding in COPD. Cease before the middle of inspiration. (b) Late or pan-inspiratory crackles: disease confined to the alveoli
88
What is the pathophysiology behind crackles/rales/crepitations?
Loss of stability in peripheral airways, causing collapse on expiration. Upon inspiration there is rapid air entry into the distal airways. This causes the abrupt opening of alveoli and of small/medium-sized bronchi containing secretions.
89
Streptococcus pneumonia is a Gram-_________ organism
Streptococcus pneumonia is a Gram-POSITIVE organism
90
State the Gram status of the 2nd and 3rd most common causes of CAP
Haemophilus influenza Moraxhella catarrhalis Both Gram-negative
91
Rapid molecular testing (e.g. PCR) for rifampicin resistance is recommended if there is a risk of...?
Rapid molecular testing (eg PCR) for rifampicin resistance is recommended if there is a risk of multidrug-resistant TB (MDR-TB)
92
Early inspiratory crackles are a characteristic finding of which disease?
COPD