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INTRODUCTION TO LOWER RESPIRATORY TRACT INFECTIONS
General Goal: To know the major mechanisms of
defense in the LRT, the major mechanisms invaders use to avoid the defenses of
the LRT, and the common modes of transmission.
Specific Educational Objectives: The student
should be able to:
1. describe most common modes of transmission of pneumonia.
3. describe defense mechanisms the body uses to protect itself
4. the mechanisms microbes use to infect the LRT.
Reading: Mosby's Color Atlas and Text of Infectious
Diseases by Christopher P. Conlon and David R. Snydman. pp. 67-76.
Lecture: Dr. Neal R. Chamberlain
A. Epidemiology of lower respiratory tract (LRT) or parenchymal respiratory
B. General Anatomy
Of the LRT infections pneumonia remains the most common infections seen
in the community and among hospitalized patients. Despite the use of antibiotics
the mortality associated with pneumonia is still quite high. In 2000 pneumonia
and influenza were the seventh leading cause of death in the United States (24.3
deaths per 100,000 population).
Approximately, 1.8 cases of pneumonia were reported for every 100 Americans in
1996. Pneumonia is also a very common case of nosocomial infections
ranking third in occurrence behind urinary tract infections and surgical
wound infections (33% of the infections acquired in the hospital).
As mentioned previously the respiratory tract is usually divided into three
The alveoli are lined with two types of cells, the Type 1 and Type 2 pneumocyte.
The Type 1 pneumocyte is a very large thin cell stretched over a very large
area. This cell can not replicate and is susceptible to a large number
of toxic insults. Type 1 pneumocytes are responsible for gas exchanges
occurring in the alveoli. The Type 2 granular pneumocyte is smaller, roughly
cuboidal cell that is usually found at the alveolar septal junctions. This
cell is responsible for the production and secretion of surfactant. The
Type 2 pneumocyte can replicate in the alveoli and will replicate to replace
damaged Type 1 pneumocytes.
C. Mechanisms of defense.
I. The Upper Respiratory tract: This includes the nose, paranasal sinuses,
II. The Respiratory Airways: This includes the trachea, bronchi, and bronchioles.
III. The Lungs: This includes the respiratory bronchioles, alveolar ducts,
alveolar sacs, and the alveoli.
Particles from 2 um to 0.2 um can go all the way down inside the alveoli
avoiding the defenses of the upper respiratory tract and the mucociliary
elevator. (Note: Most bacteria and all viruses are 2 mm
The following defense mechanisms in the alveoli protect the parenchymal
cells from invasion by microorganisms.
Once a microorganism arrives in the alveoli it can be opsonized by IgG
in the fluid lining the alveoli. These organisms will then be ingested
by the macrophage. If no specific antibody to the organism is present then
the macrophage may still be able to phagocytize the invader however, at
a slower rate. Once the microorganism is phagocytized the macrophage will
destroy the organism, if it can, and present microbial antigens on the
surface to awaiting B and T cells. Once activated the B and T cells can
produce more antibody and/or activate the macrophage. Meanwhile the macrophage
is also releasing factors that help bring in polymorphoneutrophils (PMN)
from the blood stream and initiate an inflammatory response. Along with
the PMNs come more antibodies and complement components useful in destroying
the invader. The invaders can also at this time leave the lung and get
into the general circulation. This is probably why systemic signs of infection
(fever, malaise, myalgia, etc.) occur in pneumonia.
D. Mechanisms invaders use to avoid the normal defense mechanisms of
Alveolar macrophages (the most important)
Alveolar lining fluid containing surfactant, phospholipids, neutral lipids,
IgG, IgE, IgA, secretory IgA, certain complement components, Factor B,
and other unidentified agents that maybe important in activation of alveolar
B cells, T cells, and null cells that can elicit a localized immune response
Lymphoid tissue associated with the lungs.
To kill the microorganism in the alveoli it must be phagocytized by the
alveolar macrophage. If these microbes can avoid phagocytosis or survive
once phagocytized they can survive in the lung. Microorganisms have developed
a number of ways to avoid phagocytosis. Once phagocytized certain organisms
can survive in the phagocyte.
Mechanisms used to avoid phagocytosis.
Mechanisms used to survive in the phagocyte.
Capsule production. (S. pneumoniae, H. influenza, B. anthracis, N. meningitidis,
Toxin production. These toxins could include cytotoxins, leukocidins, and
exotoxins. (examples; S. aureus produces leukocidins and cytotoxins.
P. aeruginosa produces exotoxin A which destroys cells much like the
diphtheria toxin does.)
Being too large to phagocytize. Parasites and fungi are often too large
for the phagocyte to engulf.
Replication inside cells. Viruses and Chlamydia sp. are obligate
intracellular parasites that replicate inside the cells of the lung avoiding
Mimicry. Some parasites produce surface proteins which are very similar
to host proteins or acquire host proteins and appear to the phagocyte as
self. Some bacteria produce proteins that cause host proteins to bind to
their surfaces (ex. protein A/Staphylcoccus aureus)
E. Modes of transmission
Inhibition of lysosome fusion with the phagosome. (Toxoplasma gondii,
Aspergillus sp., Chlamydia psittaci)
Escape from the phagosome. (Mycobacterium leprae, Trypanosoma cruzi,
Influenza virus escapes the phagolysosome)
Resistance to killing and digestion in the phagolysosome. (Mycobacterium
tuberculosis, Nocardia sp., Yersinia pestis)
Growth in the phagocytic cell. (M. tuberculosis, Legionella pneumophila,
Entry into the phagocyte other than by phagocytosis. Some organisms avoid
destruction by getting into the phagocyte's cytoplasm. No phagosome-lysosome
fusion occurs and the organisms can survive in the phagocyte. (Toxoplasma
gondii, some enveloped viruses)
Inhalation and aspiration are the two most common
means of acquiring an infectious pneumonia.
Inhalation of small airborne infectious particles (airborne transmission).
Most microorganisms that cause pneumonia are able to survive on airborne
droplets. These droplets can float in the air for quite a long time and
if still infectious can sometimes cause pneumonia.
Aspiration of resident naso-oropharyngeal flora or large airborne
particles after deposition in the naso-oropharynx (aspiration pneumonia).
Usually aspiration of material into the lungs occurs during sleep. Certain
people aspirate more than others during sleep and as a result have more
problems with LRT infections. Other groups of people bothered by aspiration
related LRT infections are alcohol abusers, drug abusers, and comatose
Hematogenous spread to the lung from another site of infection.
People with endocarditis, septic pelvic or jugular thrombophlebitis may
also experience LRT infections. Pneumonia acquired by hematogenous spread
to the lungs often times is bilateral and uniform. Pneumonia transmitted
by bronchogenic infection (inhalation, aspiration) are usually unilateral
and tend to localize in the lung.
Direct extension from a contiguous site of infection. Entamoeba
histolytica can cause pneumonia by direct extension from an amebic abscess
in the liver. Influenza and Respiratory Syncytial Viruses can spread from
the upper respiratory tract to the LRT via infection of the respiratory
Exogenous penetration and contamination of the lung can occur due
to accidental trauma (car accident) or surgery.
F. Pathogenesis of Pneumonia
A microorganism enters the alveoli and proceeds to grow in the rich environment
provided by the lung. Oftentimes the organism contains a capsule or is
intracellular and can avoid phagocytosis for a period of time. As a result
of tissue injury an inflammatory response occurs. Tissue injury can occur
due to exotoxins produced by a bacteria, cell lysis caused by a virus,
or death of alveolar macrophages and dumping of their lysosomal contents
in the alveoli due to growth of an organism in the phagocyte. Vascular
permeability increases and PMNs arrive at the area attempting to contain
and eliminate the organisms. Along with PMNs come many of the serum components.
Meanwhile other alveolar macrophages are being recruited to the area of
inflammation. This accumulation of microorganism, immune cells, and serum
components causes the alveoli to fill up and can result in spread to other
alveoli in close proximity. This inflammatory response is what is described
as an opacity or consolidation when viewing a roentgenograph (a X-ray film).
Not only are serum components coming into the alveoli but certain products
made by the microorganism are able to leave the lung and exert systemic
effects. Examples include endotoxin from gram negative bacteria eventually
resulting in fever and septic shock, and cell wall components of gram positive
bacteria that can eventually lead to fever production and septic shock.
All of the microbial products producing or indirectly resulting in systemic
changes have yet to be clearly determined.
The deleterious effects on the host fall into two categories:
G. Enumeration of organisms capable of causing pneumonia
Systemic effects such as fever, shock, (particularly associated with gram
negative bacteria) and wasting (chronic tuberculosis).
Interference with the ability of the lungs to carry out air exchange. This
can be due to thickening of the membrane that separates erythrocytes from
inspired air in the alveoli, and inflammation in the alveoli resulting
in regional mismatches in the ventilation and perfusion of the lungs.
The following are the organisms that can cause pneumonia. (*Note: not a
|Streptococcus pyogenes (Grp A)
| Streptococcus agalactiae (Grp B)
|Other Bacillus sp.
||Herpes Simplex Virus
||Respiratory Syncytial Virus
|Other Mycobacterium sp.
|Coxiella burnetii (Q-fever)
H. Complications of Pneumonia- Basically there are two types
1. Complications that occur during the acute phase of the infection.
2. Chronic complications
Pleural effusion: Sterile effusion into the pleural space surrounding the
Empyema: A pleural effusion that is grossly purulent (contains bacteria
and white blood cells).
Fluid and electrolyte: Dehydration and hypernatremia (high concentration
of sodium in the blood).
Hematologic: Anemia seen in chronic pneumonia, disseminated intravascular
coagulation (usually gram negative pneumonia), and thrombocytopenia (Influenza
binding to platelets).
Hepatic: Bacterial pneumonias can commonly be associated with mild elevations
of liver enzymes without evidence of liver invasion. Sometimes jaundice
can occur and can indicate a poor prognosis.
Renal: In cases of severe pulmonary infections protein catabolism markedly
increases. This results in an azotemia (nitrogenous products in the blood).
This condition is transient and renal damage does not occur (No large increase
Abnormalities in pulmonary function: Usually manifested as a decrease in
Bronchiectasis: Is a disorder characterized by irreversible destruction
and dilatation of airways.
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©2002 Neal R. Chamberlain, Ph.D., All rights reserved.