T2 L10: Respiratory infections

• lungs are constantly exposed to particulate material and microbes from the upper airway
• lower airways are usually devoid of conventional pathogens
• innate immunity

  cilia - removes debris and pathogens

  alveolar macrophages
• function of alveolar macrophages:

  secrete antimicrobials

  engulf and kill pathogens

  recruit other immune cells

  process and present antigens to T cells
• acquired immunity

  B/T cell responses

  IgA secreted by plasma cells - interferes with adherence and viral assembly
• viral rhinitis (common cold)

  upper respiratory tract infection

  rhinovirus = most common

  coronaviruses - 10-15%

  >200 viral subtypes
• viral rhinitis transmission

  hand contact

  droplet transmission

  
  

  IP 2-3 days, lasts 3-14 days
• what causes sore throat and blocked nose in colds?

  bradykinin: intranasal administration causes sore throat and nasal congestion due to vasodilation
• what causes sneezing?

  histamine-mediated - by stimulation of the trigeminal sensory nerves
• what causes nasal discharge?

  due to myeloperoxidase, changes colour with increasing number of neutrophils
• what causes you to cough?

  mediated by the vagus nerve - inflammation has to extend to larynx to trigger this
• what is responsible for systemic symptoms eg. fever?

  cytokines
• differences between cold and flu:

  flu is basically a more severe and acute cold

  
• uncomplicated influenza

  most caused by influenza A/B virus

  IP 1-4 days lasts 3-7

  abrupt onset of symptoms - fever + cough / sore throat

  acutely debilitating

  fever 38-41 c
• influenza risk groups for complications:

  immunosuppressed/ chronic conditions

  pregnancy/2 weeks postpartum

  <2yrs/>65yrs

  BMI>40
• complications associated with influenza:

  primary viral pneumonia

  secondary bacterial pneumonia

  CNS disease

  death
• recap: stages of viral pathogenesis

  Attachment

  penetration

  synthesis of new components

  assembly

  release
• how does influenza enter the cell?

  influenza virus haemagglutinin surface protein (H) binds sialic acids on cell surface glycoproteins and glycolopids in the respiratory tract, allowing it to enter the cell.
• how does the influenza virus prevent escaping virions from clumping together?

  neuraminidase (N) on surface of virus allows it to escape by cleaving sialic acid bonds
• influenza virus has a segmented genome (8 parts) so can reassort if two different viruses infect the same cell
• influenza shift and drift: antigenic drift


  neutralising antibodies against haemagglutinin block binding to cells

  mutations alter haemagglutinin epitopes so that the neutralising antibody no longer binds
• multiple reassortment events in virus genome can cause it to infect other animals eg. humans
• treatment and prevention of influenza

  active immunisation against haemagglutinin and neuraminidase

  hand hygiene and droplet precautions
• Epiglottis/ HiB

  Haemophilus influenzae b infection

  disease of adults

  symptoms include:

  drooling, dysphagia, distress

  risk of sudden complete airway obstruction

  ENT emergency
• croup/ laryngotracheobronchitis

  inflammation of the larynx, trachea and bronchi

  = upper airway obstruction, especially at the narrowed subglottic region

  parainfluenza virus most common
• croup symptoms

  barking cough, inspiratory stridor, hoarse voice

  hypoxia is a late sign and very worrying

  use of accessory muscles
• croup management

  reduce inflammation (steroids +- adrenaline)
• acute bronchitis

  lower respiratory tract infection

  damage to bronchial walls -> increased mucus production + oedema of bronchus = productive cough
• acute bronchitis symptoms

  usually viral

  assoc. with URTI symptoms

  may be wheeze/ dyspnoea

  no fever/ systemic upset

  cough continues after infection cleared as bronchial wall has to heal - may take weeks
• bronchiolitis

  acute infection of the epithelial cells lining the small airways

  results in oedema, increased mucus production, cell death

  the debris and oedema obstructs the distal airways

  disproportionate narrowing in expiration means air trapping and wheeze

  
• what is the cause of bronchiolitis?

  majority caused by RSV (respiratory syncitial virus)

  usually children <2yrs
• bronchiolitis symptoms

  cough wheeze and tachypnoea

  increased work of breathing

  fever; corzya
• bronchiolitis diagnosis and treatment

  viral nose/throat swab or respiratory secretions for RT-PCR

  treatment = supportive care
• pneumonia - pathophysiology

  pneumonia = infection of the lung parenchyma

  alveoli full of inflammation = blocks oxygen transfer
• pneumonia symptoms

  fever, breathlessness, cough, sputum production

  hypoxia, increased respiratory rate

  pleuritic chest pain

  sepsis
• radiology - diagnosis of pneumonia

  requires infiltrates on a plain CXR with supporting clinical features

  consolidation: alveoli and bronchioles completely filled with inflammatory debris/pus/pathogens

  heart borders or diaphragm obscured due to the loss of solid-gas interface

  air bronchograms- air in larger bronchi outlined by surrounding consolidation
• classifications- most useful:

  community vs hospital-acquired - useful as pathogens involved differ in their % contribution
• community-acquired pneumonia pathogens

  Streptococcus pneumoniae

  Haemophilus influenzae

  Mycoplasma pneumoniae

  Legionella pneumophila

  Staphylococcus aureus
• streptococcus pneumoniae 


  commonest organism - gram positive diplococci, acquired in nasopharynx

  asymptomatic carriage in 40-50% ppl
• risk factors for strep. pneumoniae

  alcohol dependency, respiratory disease, smokers, hyposplenism, chronic heart disease

  HIV - 50 o 100 fold increase in invasive pneumococcal disease