Respiratory Tract Infections

Question 1

Lung bugs

Answer 1

Streptococcus pneumoniae
Mycobacterium tuberculosis
Legionella pneumophila

Lower airway usually devoid of conventional pathogens

Question 2

Innate immunity

Answer 2

Cilia – mucociliary escalator removing debris and pathogens

Alveolar macrophages  
secrete antimicrobials 
engulf and kill pathogens
recruit other immune cells
process and present antigens to T cells

Question 3

Acquired immunity

Answer 3

B cell/T cell responses – essential for intracellular pathogens, inc mycobacteria, viruses and fungi
IgA secreted by plasma cells interferes with adherence and viral assembly

IgA forms an additional epithelial protective barrier, which prevents microbial adherence to the epithelial surface and inhibits certain viral infections (influenza) by interfering with their assembling processes

Question 4

Response to infection

Answer 4

Inflammation

Macro - redness, swelling, heat, pain and loss of function
Micro = vasodilation, increased vascular permeability and inflammatory cell infiltration

Question 5

Respiratory tract infections

Answer 5

Rhinitis 
Sinusitis
Pharyngitis
Tonsillitis
Laryngitis

Bronchitis
Bronchiolitis
Pneumonia
Pulmonary tuberculosis
Pulmonary abscesses
Empyema

Question 6

URTIs - transmission

Answer 6

hand contact (direct or indirect)

droplet transmission from sneezing / coughing

remain viable for up to 2 hours on skin or several hours on surfaces

Question 7

URTIs

Answer 7

> 200 viral subtypes associated

Rhinovirus = most common

Question 8

Cold

Answer 8

Appears gradually
Affects mainly your nose and throat
Makes you feel unwell but you’re okay to carry on as normal – for example, go to work
Usually no fever

Question 9

Flu

Answer 9

Appears quickly within a few hours
Affects more than just your nose and throat
Makes you feel exhausted and too unwell to carry on as normal
High fevers

Question 10

Influenza

Answer 10

Caused by Influenza A or B virus.

Occurs in outbreaks and epidemics worldwide; usually in winter season, so swaps hemispheres over the course of the year.

Question 11

Uncomplicated influenza

Answer 11

IP 1-4 days
Abrupt onset of fever, headache, myalgia and malaise.
+ cough, sore throat, nasal discharge
Acutely debilitating.
Fever 38-41OC; otherwise examination often unremarkable

Question 12

Influenza complications

Answer 12

Primary viral pneumonia
Secondary bacterial pneumonia
CNS disease

Question 13

Risk groups for complications

Answer 13

Immunosuppression or chronic medical conditions
Pregnancy or 2 weeks postpartum
Age <2y or >65y
BMI >40

Question 14

3 problems facing virus

Answer 14

It must know how to replicate inside a cell

It must move from one infected cell to a new cell (and a new host) in order to persist in nature

It must develop mechanisms to evade host defences

Question 15

Influenza virus

Answer 15

Hemogglutinin surface protein (H) binds sialic acid receptors on host cells in the respiratory tract. This allows the influenza virus to enter the cell.

The neuraminidase (N) on the surface of the virus allows the virus to escape by cleaving sialic acid bonds – otherwise the escaping virions all clump together.

The influenza virus has a segmented genome (8 parts) so can reassort if 2 different viruses infect the same cell.

Question 16

Pneumonia

Answer 16

infection of the lung parenchyma

Alveoli inflammation blocks oxygen transfer

Question 17

Pneumonia symptoms

Answer 17

Fever, breathlessness, cough, sputum production;
Hypoxia, increased respiratory rate;
Pleuritic chest pain
Sepsis

Question 18

Pneumonia radiology

Answer 18

Consolidation
May see air bronchograms
Heart borders or diaphragm obscured due to loss of solid-gas interface

Interstitial infiltrates
± cavitation

Question 19

Classifications

Answer 19

Typical versus atypical – but not very helpful, as there is no feature in an individual patient that helps distinguish between them.

Community versus hospital acquired = much more useful, as the pathogens involved differ in their % contribution

Lobar versus bronchopneumonia – also not very helpful; descriptive, but doesn’t help managment

Question 20

Pneumonia pathogens

Answer 20

Streptococcus pneumoniae 
Haemophilus influenzae
Mycoplasma pneumoniae 
Legionella pneumophila 
Staphylococcus aureus
Respiratory viruses probably responsible for ~1/3
Pneumocystis jirovecii in cell mediated immunodeficiency
Aspergillus fumigatus

Question 21

Streptococcus pneumoniae

Answer 21

Gram positive cocci

RFs
Alcoholics, respiratory disease, smokers, hyposplenism
HIV – 50- to 100-fold increase in invasive pneumococcal disease in HIV+

Acquired in nasopharynx
Asymptomatic carriage in 40-50%
smokers>non-smokers

Prevention – vaccine

Question 22

Pneumococcal disease diagnosis

Answer 22

Easy to grow in lab from sputum cultures

Blood cultures: (<1% patients +ve)
Higher mortality
Extra-pulmonary disease
Meningitis
Septic arthritis
Empyema
↑alcohol intake

Question 23

Mycoplasma pneumoniae

Answer 23

Commonest cause of ambulatory ‘atypical pneumonia’
Classically young patient, vague constitutional upset, several weeks
Extrapulmonary symptoms very common
Skin, CNS and heart

Lacks cell wall
resistant to penicillins
cannot grow on normal lab plates

Question 24

Mycoplasma pneumoniae diagnosis

Answer 24

Diagnosis by PCR of throat swab (VTS)

Treatment: macrolides or tetracyclines

Question 25

Legionella pneumophila

Answer 25

2-9% CAP (more common in UK than Europe)
Cigarettes and chronic lung disease
Can occur as sporadic infection or cause outbreaks associated with a contaminated water source

Can cause severe, life threatening infection
Initial mild headache, then high fevers, myalgia, dyspnoea, confusion, dry cough and GI upset
Extra-pulmonary complications ++ inc lymphopenia and low Na

Question 26

Legionella pneumophila - diagnosis

Answer 26

Don’t grow on routine culture – need special conditions, and longer
Urinary legionella antigen
Treatment: macrolides or quinolones

Question 27

Hospital acquired pneumonia

Answer 27

New onset at least >48 hours since admission.

Hospitalised patients become colonised
with hospital bacteria

These may either be intrinsically more resistant to antibiotics, or have acquired resistance mechanisms.

Either way, broader spectrum antibiotics are used empirically.

Question 28

Pneumonia complications - general

Answer 28

Sepsis (Multi organ failure)

Respiratory failure

Question 29

Pneumonia complications - local

Answer 29

Pleural effusion 
Emphysema ?
Lung abscess 
Collapse 
Post infection bronchiectasis

Question 30

Pathology of pneumonia

Answer 30

Aerobic bacillus

Divides every 16-20 hours (slow) – lab extends culture to 56 days

Cell wall, but lacks phospholipid outer membrane
Does not stain strongly with Gram stain (weakly positive)
Retains stains after treatment with acids

Referred to as acid fast bacillus (AFB)

Special stains – Ziehl-Neelsen or auramine-rhodamine

Question 31

Diagnosis of TB

Answer 31

Active TB
Identify the infected area
Isolate the organism
Obtain information regarding susceptibility to antibacterials

Latent infection
Identify immune response to TB proteins or TB-specific antigens

Question 32

TB step by step

Answer 32

Infection is initiated by the inhalation of aerosol droplets that contain bacteria.

The initial stages of infection are characterized by innate immune responses that involve the recruitment of inflammatory cells to the lung.

Following bacterial dissemination to the draining lymph node, dendritic cell presentation of bacterial antigens leads to T cell priming and triggers an expansion of antigen-specific T cells, which are recruited to the lung.

The recruitment of T cells, B cells, activated macrophages and other leukocytes leads to the establishment of granulomas, which can contain Mycobacterium tuberculosis

Question 33

TB management

Answer 33

Cure active disease
Reduce spread
Prevent reactivation

By… 1. prompt and adequate treatment;

     2. appropriate source isolation; 
     3. by contact tracing