lecture 5 Flashcards
To understand the relationship between the host defences (respiratory tract), infecting organisms (bacteria, viruses, fungi), and chemicals or trauma in lung injury. The general mechanisms causing acute and chronic inflammation and changes is cells and tissues due to the host response. 1. lung defences and loss of defences 2. pneumonia syndromes 3. inflammatory responses 4. acute inflammation in the lung - bacterial pneumonia - ALI - ARDS 5. chronic inflammation features
What is the normal structure of the lung?
- airways:
- mouth
- nose
- pharynx
- larynx
- trachea (anterior C-shaped plates of cartilage with posterior smooth muscle, mucous glands)
- bronchi (discontinuous foci of cartilage with smooth muscle, mucous glands)
- bronchioles (no cartilage or submucosal mucous glands, clara cells secreting proteinaceous fluid, ciliated epithelium)
- alveolar duct (flat epithelium, no glands, no cilia)
- alveoli (type I and II pneumocytes)
- branching of airways into alveoli is matched with a high level of capillaries and capillary networks that absorb oxygen from the alveolar cells
- you breath whatever is in the air
- each day constantly exposed to dust, chemicals, micro-organisms - breath 10,000 litres of air each day
- most individuals cope with this quite well as there are first line defences
- distal lung is normally quite sterile
- ciliated cells in bronchi and bronchioles help to eject a lot of the debris that we breathe in
- goblet cells that produce mucus: protective barrier against infection
What is the filtering capacity of different regions of the lung?
- 5-10µ - nose/upper RT
- 3-5µ - trachea & bronchi
- <2µ - alveoli
Where do infections commonly occur in the lung? Where do dangerous infections tend to occur?
- most common infections seem to occur in bronchi/bronchioles (e.g. bronchitis)
- most dangerous infections seem to occur in alveoli - problems with transferring oxygen into blood
What features of the normal lung are important for gases to exchange efficiently?
- alveoli walls must be very thin (95% of alveolar surface area)
- massive surface area (about 35 times the surface area of the body)
What is the normal alveolar structure?
- critical anatomical area of the lung
- Type I pneumocytes cover 95% of the alveolar surface, very thin to allow for oxygen transfer
- Type II cells synthesise surfactant and are involved in the repair of alveolar epithelium through their ability to give rise to type I cells, surfactant gives the alveolar their structure, allows for transfer of oxygen and prevents them from collapsing
- resident macrophages - small numbers in homeostatic state
- capillaries (endothelial cells)
- rare monocytes/other WBCs
What happens when you have injury (infection) of the lung?
- acute inflammatory response/s (rapid)
- pneumonia
3a. recovery
3b. chronic disease
3c. death
Which areas of the lung are affected by pneumonia?
- pneumonias are respiratory disorders involving acute inflammation of the lung structures, such as the alveoli and bronchioles
How can we classify pneumonia?
According to causative agent:
Infectious:
- bacterial (the most common cause of pneumonia)
- viral pneumonia
- fungal pneumonia (rare)
Non-infectious (usually cause A.L.I)
- chemical pneumonia (ingestion or inhalation of irritating substance)
- inhalation pneumonia (aspiration pneumonia) (breathing in high acid gastric contents)
How does one get pneumonia?
- the development of pneumonia is facilitated by an exceedingly virulent organism, large inoculum, and impaired host defences
What are the normal host defences in the lung?
Innate:
- mucus blanket - mucu-ciliary escalator + cough reflex
- phagocytosis - alveolar macrophages
- phagocytosis - recruited neutrophils
- complement - C3b - MAC
- draining lymph nodes - initiation of immune response
Acquired:
- secreted IgA
- IgM and IgG in alv fluid
- activate complement
- opsonise - accumulation of T cells - viral infections
How can lung defences be reduced?
- pneumonia occurs when these defences are impaired &/or host resistance decreased
- e.g. smoking, chronic alcohol, viral infection, chronic disease, treatment with immunosuppressive agents, diabetes, malnutrition, wasting diseases, interferences with phagocytic ability of alveolar macrophages (genetic/acquired) etc
- one type of RT infection pre-disposes to another
- many with terminal disease –> fatal pneumonia
- antibiotic resistant bacteria and invasive procedures –> spread
- loss/suppression of cough reflex via - coma, anaesthesia, neuromuscular disorders, drugs, chest pain - can lead to aspiration of gastric contents
- injury to muco-ciliary apparatus
via - T-smoke, viral infection, inhalation of hot/corrosive gases, genetic abnormalities (e.g. immotile cilia syndrome) - interference with phagocytic/anti-bacterial action of alveolar macrophages
via - alcohol, T smoke, anoxia, or O2 intoxication, genetic abnormality - accumultion of secretions - e.g. cystic fibrosis, bronchial obstruction (e.g. tumour), stroke
- pulmonary congestion or oedema: due to chronic heart disease
How is pneumonia an opportunistic infection?
- usually occurs as a secondary infection in people who have other diseases/things that compromise their immune system e.g.
- AIDS
- alcoholics
- transplant immunosuppression
- pregnancy
- alcoholism
- cystic fibrosis
- autoimmune disease
- burns
- cancer
- chemotherapy
- old or young age
- chronic steroids
- diabetes
- some bacteria seem to cause widespread damage to the lungs (e.g. cytomegalovirus) while others seem to cause focal infection (e.g. gram-negative rods)
What is the number one killer of children under 5 in the world?
Pneumonia
What are some specific subtypes of pneumonia?
Community-acquired acute pneumonia
- e.g. Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila
- large volume of inflammatory exudate in alveoli and airways
Community-acquired atypical pneumonia
e. g. Mycoplasma, Chlamydia, viruses (influenza A & B)
- smaller amounts of exudate - patchy - in alveolar interstitium
Nosocomical Pneumonia (hospital acquired)
- e.g. Enterovactiaceae: Klebsiella pneumoniae, E. coli, Pseudomonas pneumoniae, Staphlococcus aureus (penicillin-resistant)
- due to chronic disease &/or immunosuppression, invasive procedures, resistant organisms
What are the differences between some of the pneumonia syndromes?
Chronic pneumonia
- fungal species e.g. Nocardia
- Intracellular bacteria e.g. Mycobacterium tuberculosis
- often granulomatous inflammatory response
Aspiration pneumonia (necrotising)
- most often in debilitated patients
- those who aspirate gastric contents
- chemical and bacterial
Pneumonia in immunocompromised host
- Cytomegalovirus
- Pneumocystis
- Fungal species, e.g. candida, aspergillus
- chronic disease, immunosuppression, chemotherapy, irradiation
What organ is most affected by acute inflammation?
- the lungs - more than any other organ
