Lecture 6: Respiratory Pathology (Pneumonia and Acute Lung Injury)

Question 1

Describe the normal alveolar structure.

Answer 1

Normal alveolar structure consists of:

• Type I pneumocytes: cover 95% of the alveolar surface
• Type II pneumocytes: synthesize surfactant and involves in the repair of alveolar epithelium through their ability to differentiate into type I cells
• Tissue-resident macrophages
• Capillaries (endothelial cell)

Question 2

Recall the microscopic image of a normal alveolar structure

Answer 2

Question 3

Define pneumonia.

Answer 3

Pneumonia are respiratory disorders involving acute inflammation of the lung structures, mainly the alveoli and bronchioles

Question 4

Mention the classification of pneumonia.

Answer 4

• According to the causative agent:
  
  • Infectious
    
    • Bacterial (most common cause of pneumonia)
    • Viral pneumonia
    • Fungal pneumonia
  • Non-infectious (usually cause Acute Lung Injury)
    
    • Chemical pneumonia (ingestion/inhalation of irrating substance)
    • Inhalation pneumonia (aspiration pneumonia)

Question 5

Mention an example of a highly dangerous lung pathogen.

Answer 5

Question 6

Infectious pneumonia is an ____________ infection. Explain it.

Answer 6

Penumonia is an opportunistic infection. It most often affects people with impaired host defences, i.e. immunocompromised individuals.

Question 7

Mention the host defences in the respiratory tract.

Answer 7

• Muco-ciliary clearance
  
  • Goblet cell: mucus production
  • Ciliated cell: mucus transport
  • Lamina Propria: layer between the epithelial and muscle layer; harbour macrophages
• Surfactant proteins:
  
  • produced by Type II pneumocytes
  • protect airways from infection
  • maintain alveolar integrity - reduce surface tension
• Alveolar macrophages

Question 8

_________________ influences efficiency of first-line macrophage-mediated phagocytosis.

Answer 8

Infectious bacterial dose

Question 9

Mention examples of impaired lung defences.

Answer 9

• Loss/suppression of cough reflex
  
  • can lead to aspiration of gastric contents
  • patients inc oma, anaesthesia, NMD, drugs, chest pain
• Injury to mucociliary apparatus
  
  • long-term smoking, viral infection, genetic disease (CF)
• Pulmonary congestion or oedema: due to chronic heart disease
• Low IgG &/ IgA

Question 10

Differentiate between acute and chronic inflammation in the upper respiratory tract.

Answer 10

Question 11

Describe the mechanism behind the thickening of bronchiole in chronic inflammation.

Answer 11

Due to the prolonged process of injury and healing, this leads to the continuous release of GFs. This GF, other than assisting in the healing process, also leads the overproliferation of smooth muscle cells - thickening the bronchiole.

This change may also be in response to increased pressure to the lung - requiring thicker muscle layers to continue function.

Question 12

Describe the classification of acute inflammation in the lung.

Answer 12

Question 13

Describe the time course of lung acute inflammation.

Answer 13

Question 14

Describe the histopathology of early acute lung inflammation.

Answer 14

Question 15

Describe the histopathology of a later case of acute lung inflammation.

Answer 15

Question 16

What is the function of the pores of Kohn?

Answer 16

The pores allow the passage of other materials such as fluid and bacteria, which is an important mechanism of spread of infection in lobar pneumonia and spread of fibrin in the grey hepatisation phase of recovery from the same. They also equalize the pressure in adjacent alveoli and, combined with increased distribution of surfactant, thus play an important role in prevention of collapse of the lung.

Question 17

What is lung hepatization?

Answer 17

It is a state of the lungs when gorged with effuse matter, so that they are no longer pervious to the air. Red hepatization is when there are red blood cells, neutrophils, and fibrin in the pulmonary alveolus/ alveoli; it precedes gray hepatization, where the red cells have been broken down leaving a fibrinosuppurative exudate.

Question 18

Describe the complication because of acute inflammation in the lung.

Answer 18

Results in:

• tissue destruction and necrosis
• spread of infection and inflammation of the pleural cavity (pleurisy)
• bacteraemic dissemination (brian, heart, kidneys)

Symptoms:

• malaise, fever, chills
• chest pain secondary to pleurisy
• ARDS (Acute Respiratory Distress Syndrome)

Question 19

Recall the outcomes of acute versus chronic inflammation.

Answer 19

Question 20

Describe the histopathology of chronic inflammation in the lung.

Answer 20

Question 21

Describe ARDS.

Answer 21

Question 22

Mention the common causes of ARDS.

Answer 22

Question 23

How is ARDS diagnosed?

Answer 23

Question 24

Compare a normal alveolus and an injured alveolus in the acute phase of ALI/ARDS.

Answer 24

Question 25

Describe the progression of ARDS.

Answer 25

1. Exudative Phase (Acute)
   
   • Day 1: interstitial/alveolar oedema, degenerative changes in type I pneumocytes - start of interstitial infiltrate (lymphocytes, macrophages)
   • Day 2: breakdown of type I cells - bare basement membrane, hyaline membrane begins to form
   • Day 4-5: peak of hyaline membrane formation = poor gas exchange
   • Day 7: peak of interstitial inflammatory infiltrate; type 2 pneumocytes proliferate and spread along basement membrane; thrombi in alveolar capillaries
2. Organising Phase (Slower)
   
   • Day 14: Interstitial fibroblasts proliferate -producing collagen
     
     • Interstitial inflammation and Type II hyperplasia persist
     • Macrophages breakdown hyaline membrane and debris

Question 26

Recall the histopathology of the organising phase of ARDS.

Answer 26

Question 27

Mention the possible outcomes of ARDS.

Answer 27

• Resolution: complete recovery and restoration of normal lung function
  
  • alveolar exudate and hyaline membrane reabsorbed
  • normal alveolar epithelium restored
  • fibroblast proliferation ceases
  • extra collagen metabolised
• End-stage fibrosis
  
  • exudate associated with tissue destruction
  • large amount of scar tissue remodelled (hyaline membranes)
  • lung architecture remodelled -multiple cyst-like spaces (honeycomb lungs)
  • spaces separated by fibrous tissue, type II pneumocytes, bronchiolar epithelium or squamous cells.

Question 28

Mention the treatments of ARDS.

Answer 28

Question 29

Mention the possible drug target for ALI/ARDS.

Answer 29