URI Lower - Diebel Handout - Background

Question 1

General Anatomy of the lungs:

Answer 1

Respiratory bronchioles –> alveolar ducts –> alveolar sacs –> Alveoli which are lined with both Type I pneumocytes and Type II pneumocytes

Question 2

What is the most common LRTI seen in community and hospital?

Answer 2

Pneumonia

Question 3

What is a very common cause of nosocomial infections (ranking third behind UTI and surgical wounds)?

Answer 3

Pneumonia

Question 4

What are Type I pneumocytes?

Answer 4

• Very large, thin cell
• Responsible for gas exchanges in alveoli
• Cannot replicate
• Susceptible to many toxic insults

Question 5

What are Type II granular pneumocytes?

Answer 5

• Smaller and usually found at the alveolar septal junctions
• Can replicate and will replace damaged Type I pneumocytes
• Responsible for production and secretion of surfactant

Question 6

What sized particles can go down the alveoli and avoid the defenses of the URT and mucociliary elevator?

Answer 6

2um to 0.2 um

most bacteria and all viruses are 2 um and smaller

Question 7

What further defense mechanisms are in place to deal with small bacterial and viral pathogens?

Answer 7

• Presence of alveolar macrophages (most IMP)
• Complement components
• Alveolar lining fluid containing surfactant
• Phospholipids
• Neutral lipids
• IgG, IgE, IgA, secretory IgA, Factor B
• B cells and T cells that elicit localized immune response

Question 8

What happens to a microorganism when it arrives in the alveoli?

Answer 8

It can be opsonized by IgG facilitating the ingestion of the microorganism by alveolar macrophages.
–> if no specific antibody present, macrophage might still be able to phagocytize, just at a slower rate

Question 9

What does a macrophage do after the microorganism has been destroyed?

Answer 9

The macrophage will present microbial antigens on its surface to awaiting B and T cells.

Question 10

What happens after the macrophages present to B and T cells?

Answer 10

B and T cells are activated and will produce more antibody and further activate more macrophages. At the same time alveolar macrophages are releasing factors that initiate an inflammatory response

Question 11

What two things must a microorganism be able to do in order to survive in the lung?

Answer 11

1. Avoid phagocytosis

2. Survive in macrophages

Question 12

What are five mechanisms used by organisms to avoid phagocytosis?

Answer 12

1. Capsule production (S. pneumoniae, H. influenza)
2. Toxin production including cytotoxins, luekocidins, and exotoxins
3. Parasites and fungi are often too large for the phagocytes to engulf.
4. Replication inside the cells: viruses and some bacteria are obligate intracellular parasites that replicate inside the cells of the lung avoiding the phagocytes.
5. Mimicry: soem parasites produce surface protein which are very similar to host proteins of acquire host proteins to appear to the phagocytes as self. Some bacteria produce proteins that cause host proteins to bind to their surfaces.

Question 13

What are four mechanisms used by organisms to survive in the phagocyte?

Answer 13

1. Inhibition of lysosome fusion with the phagosome.
2. Escape from the phagosome (Influenza virus does this)
3. Resistance to killing and digestion in the phagolysosome.
4. Growth in the phagocytic cell (Legionella pneumophila)

Question 14

What are five modes of transmission for LRT infections?

Answer 14

1. Inhalation
2. Aspiration
3. Hematogenous spread
4. Direct extension
5. Exogenous penetration and contamination

Question 15

How does inhalation lead to infection?

Answer 15

Inhalation of small airborne infectious particles (airborne transmission)

Question 16

How does aspiration lead to infection?

Answer 16

Aspiration of resident naso-oropharyngeal flora or large airborne particles after deposition in the naso-oropharynx (aspiration pneumonia). Usually aspiration occurs during sleep.

Question 17

How does hematogenous spread lead to infection?

Answer 17

Pneumonia acquired by hematogenous spread to the lung from another site of infection often times is bilateral and uniform. Pneumonia transmitted by bronchogenic infection (inhalation, aspiration) are usually unilateral and tend to localize in the lung.

Question 18

How does direct extension lead to infection?

Answer 18

Direct extension from a contiguous site of infection. Influenza and Respiratory Syncytial Viruses can spread from the URT to the LRT via infection of the respiratory epithelium.

Question 19

How does exogenous penetration and contamination of the lung occur?

Answer 19

It can occur due to accidental trauma (car accident) or surgery.

Question 20

What are the two most common means of acquiring infectious pneumonia?

Answer 20

• Inhalation

- Aspiration

Question 21

What is the general pathogenesis of pneumonia?

Answer 21

1. Microorganisms enters alveoli
2. Microorganism grows!
3. Localized tissue injury
4. Increased vascular permeability
5. PMNs arrive to help kill organism
6. Alveolar macrophages recruited
7. All these things fill alveoli (microorganism, immune cells, serum components)
8. Infection overflows and spreads to other alveoli in close proximity

Question 22

What is it that you see on a chest x-ray of pneumonia?

Answer 22

The inflammatory response is what is described as an opacity or consolidation when viewing a CXR.

Question 23

How can pneumonia lead to fever and septic shock?

Answer 23

Endotoxin from gram (-) bacteria can be released into the system that can eventually result in fever and septic shock.

Question 24

What are the two general types of damage caused to the host in pneumonia?

Answer 24

1. Systemic effects: fever, shock, wasting (chronic tuberculosis)
2. Interference with the ability of the lungs to carry out air exchange