L6 14 Mar 2019

Question 1

normal lung structure

Answer 1

• Trachea (lined with mucous gland with mucosa - surrounded by cartilage and smooth muscle)
• Bronchus
• Bronchiole
• Alveoli

Question 2

normal alvelolar structure

Answer 2

• Type 1 pneumocytes: v. thin, 95% of alveolar surface, for gas exchange
• Type 2 pneumocytes: synth surfactants - involved in repair of alveolar epithelium via ability to give rise to type 1 pneumocytes
• Resident macrophages
• Capillaries
• Macrophages and other WBCs

Question 3

pneumonia

Answer 3

respiratory disorder w/ acute inflammation of lung structure, mainly alveoli and bronchioles

Question 4

classification of pneumonia by causative agent

Answer 4

• infectious: bacterial, viral, fungal
• non-infectious (usually ALI): chemical, inhalation

Question 5

pneumonia syndromes

Answer 5

• community acquired: usually streptococcus pneumoniae and atypical bacteria (mycoplasma, chlamydia and legionella) or viral
• hospital acquired: much larger spectrum of pathogens, esp, bacterial ➡️ more difficult to treat

Question 6

Causes of adult community acquired pneumonia

Answer 6

• Streptococcus pneumoniae 48%
• influenza 13%
• Chlamydia pneumoniae13%
• Unknown 20%

Question 7

Streptococcus pneumoniae

Answer 7

• part of normal flora
• most dangerous lung infection and 2nd most common bacterial cause of death

Question 8

Streptococcus pneumoniae infections

Answer 8

• Nasopharyngeal commensal: 10% adults and 50% infants
• Can cause: otitis media (mortality 0%), meningitis (mortality 20%)
• Aspiration➡️pneumonia <75 per 100 000 colonisation
• Septicaemia➡️ (after pneumonia) 1 in 25 (mortality 20%)

Question 9

infectious pneumonia- AT RISK INDIVIDUALS

Answer 9

• people with impaired host defences (immunocompromised individuals)
• People with: AIDS, alcoholics, transplant immunosupression, pregnancy, cystic fibrosis, autoimmune, burns, cancer (chemo), v. old/young, chronic steroid, long-term diabetes

Question 10

lung defences

Answer 10

• mucociliary clearance: ciliated transport
• goblet cell w/ mucus production
• lamina propria: below epithelial cells and contains resident immune cells
• Surfactant proteins: protect airways from infection and maintains alveolar integrity - reduce surface tension in air, liquid interface ➡️ air

Question 11

lung defences: immune response to S. pneumoniae

Answer 11

1. colonisation: physical defences, mucosal proteins, IgA (opsonisation to complement mediation) and IgG, phagocytes
2. early lung infection: physical defences, mucosal proteins, alveolar macrophages activated (releases cytokines)
3. established pneumonia: inflammatory exudate (drowns alveoli), phagocytes - neutrophils, CD4 and CD8 lymphocytes
4. septicaemia: complement, circulating phagocytes: macrophages

Question 12

alveolar macrophages (AMs)

Answer 12

• first-line primary phagocytes in innate immune system
• large range of receptros for: direct interaction w/ bacteria and indirect modulation of innate and adaptive immune systems

Question 13

low dose vs. high dose of infectious bacteria on first line macrophage-mediated phagocytosis

Answer 13

• low dose: <10⁴ –> macrophage kills all bacteria within the hour
• high dose: macrophage is overwhelmed, bacteria continues to spread

Question 14

factors that affect bacterial clearance

Answer 14

• bacterial factors: low inoculum (# of pathogen), low virulence strain (how dangerous/how well they can hide)
• host factors: epithelium integrity, efficient alveolar macrophages, IgA and IgG concentration

Question 15

impaired lung defences

Answer 15

• loss/suppresion of cough reflex
• injury to muco-ciliary apparatus
• interference with phagocytic/anti-bacterial action of alveolar macrophages
• accumulation of secretions
• pulmonary congestion or oedema
• low IgG and/or IgA

Question 16

how does premature birth affect lung defence?

Answer 16

not all surfactant proteins are produced until late stage embryology

Question 17

inflammation in upper respiratory tract

Answer 17

• bronchiole surrounded by WBCs
• thickening of bronchiole –> problem in air flow and also tension stress –> smooth muscle cells proliferate to stretch out bronchiole

Question 18

bronchopneumonia

Answer 18

• acute suppurative inflammation
• often multilobular, freq. bilateral and basal - secretions tend to gravitate towards the lower lobes
• neutrophil rich exudate in bronchi, bronchioles and adjacent alveolar spaces
• patchy anatomy in the lung

Question 19

lobar pneumonia

Answer 19

affects the whole lobe

1. congestion: vascular engorgement, intra-alveolar fluid, numerous bacteria
2. red hepatisation: neutrophils, red cells and fibrin fill alveolar spaces
3. grey hepatisation: disintegration of red cells, fibrosuppurative exudate persists
4. resolution: exudate broken down –> produces granular, semifluid debris –> undergoes organisation = fibrinous thickening or permanent adhesions

Question 20

acute inflammation time course

Answer 20

1. 1 - 2 days: lung heavy, full of blood - oedema
2. 2 - 4 days: lung red, heavy, full of liquid and some fibrin - stasis and congestion
3. 4 - 8 days: lung solid, heavy, grey-white alveoli full of fibrin and neutrophils, red cells disintegrate
4. > 8 days: RESOLUTION - exudate break down and removal in a healthy person –> where phlegm comes from

Question 21

acute inflammation in lung: histology

Answer 21

• normal lung: very thin blood vessels + no cells in alveoli
• vascular congestion and stasis: large blockage of red –> congested blood vessels
• leukocyte infiltrate: large numbers of infiltrating neutrophils in alveoli
• neutrophil exudate: congested capillaries and exudate in alveoli - no gas exchange - red hepatisation
• pores of Kohn: little connections between alveoli, as one alveolus becomes swollen, some of the exudate will infect close healthy alveolus via pores of Kohn
• organisating pneumonia: transformation of exudate to fibrous masses - infiltrated by macrophages and fibroblasts

Question 22

complications with lobar pneumonia/acute inflammation in lung

Answer 22

• tissue destruction and necrosis
• spread of infection and inflammation to pleural cavity: pleurisy
• bacteraemic dissemination: endocarditis, pericarditis, meningitis, nephritis

Question 23

symptoms of complications with lobar pneumonia/acute inflammation in lung

Answer 23

• acute onset, malaise, fever, chills, productive cough
• chest pain secondary to pleurisy
• ARDS –> if symptoms aren’t relieved

Question 24

how can symptoms of complications with lobar pneumonia/acute inflammation in lung be aleviated?

Answer 24

• corticosteroids - if severe
• antibiotics - need to rapidly ID what bacteria it is to be able to administer appropriate antibiotic

Question 25

ARDS

Answer 25

acute respiratory distress syndrome: rapid onset of loss of lung function - can’t breathe properly/can’t exchange gas efficiently

Question 26

histopathology of chronic inflammation in lung

Answer 26

• collection of chronic inflammatory cells - clustered around fibrous tissue
• no type I pneumocytes –> cuboidal epithelium - oxygen exchange problems
• collagen: rigid lung, can’t stretch to take in normal amount of oxygen

Question 27

acute lung injury

Answer 27

• AKA: ARDS, shock lung, traumatic wet lungs
• diffuse alveolar damage: high mortality (40-60%)
• due to damage of: alveolar capillaries, epithelium and surfactant layer
• can be due to many reasons, usually direct injury to lung (direct chemical exposure and trauma), but also severe infectious end-stage pneumonia

Question 28

common causes of ARDS

Answer 28

• gastric aspiration
• pulmonary contusion, penetrating lung injury
• ionising radiation
• near drowning
• inhalation injury e.g. NO₂, SO₂, Cl₂, smoke
• reperfusion pulmonary oedema after lung collapse/transplant

Question 29

What are the key factors in diagnosing for ARDS?

Answer 29

• timing: always acute onset of respiratory failure
• location: (almost) always seen as bilateral infiltrate on CXR

Question 30

damages to alveolus during acute phase of ALI/ARDS

Answer 30

• rapid death of bronchila epithelium
• inactivated surfactants fall away
• type I pneumocytes die –> necrosis e.g. from toxic gases
  
  • cause cellular debris
• some fibrosis begins
• innate immune response storm: causes more problems

Question 31

ARDS progression and morphology

phase 1: exudative (acute)

Answer 31

• day 1: interstitial/alveolar oedema, lots of cell death of parenchymal cells; lymphocytes, plasma cells and macrophages enter
• day 2: sloughing of type 1 cells: basement membrane is exposed, hyaline membrane starts to form
• day 4-5: peak of hyaline membrane formation
• day 7: peak of interstitial inflammatory infiltrate; type 2 pneumocytes proliferate and spread along basement membrane, thrombi in aleveolar capillaries and pulmonary arterioles

Question 32

hyaline membrane

Answer 32

lining of “inappropriate” material: dead cells + proteins = hyaline membrane = very poor gas exchange

Question 33

ARDS progression and morphology

phase 2: organising phase (slower)

Answer 33

• macrophages breakdown hyaline membrane and debris
• > day 14: interstitial fibroblasts proliferate and produce collagen

Question 34

if one survives ARDS, then what are the two possible outcomes?

Answer 34

1. resolution OR
2. end-stage fibrosis (more often)

Question 35

resolution of ARDS

Answer 35

= complete recovery and restoration of normal lung function

• alveolar exudate and hyaline membrane is resorbed
• normal alveolar epithelium restored
• fibroblast proliferation ceases
• extra collagen metabolised
• requires:
  
  • Na⁺/K⁺-ATPase = sodium pump
  • ENaC = epithelial sodium channel
  • Aquaporins: water transport channels

Question 36

end-stage fibrosis in ARDS

Answer 36

• large amount of scar tissue produced
• lung architecture remodelled (loss of branching): cyst like spaces = “honeycomb lung”
• spaces separated from each other by fibrous tissue, lined with type II pneumocytes, bronchiolar epitheliuim or squamous cells

Question 37

treatment of ARDS

Answer 37

• mechanical ventilation
• inhalation of vasodilator, e.g. NO
• high O₂ concentrations - but not too high (toxic)
• surfactant therapy
• anti-inflammatory drugs - glucocorticoids
• w/ treatment: mortality is still high (40-60%)
• stem cell treatment?