Download pulmonary infections - University of Yeditepe Faculty of Medicine

PULMONARY
INFECTIONS
Prof.Dr.Ferda ÖZKAN
Normal Lung
The lungs are constructed to
carry out their cardinal
function: the exchange of gases
between inspired air and blood.
Normal Lung
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The respiratory system is an outgrowth from
the ventral wall of the foregut.
The midline trachea develops two lateral
outpocketings, the lung buds.
The right lung bud eventually divides into
three branches-the main bronchi-and the left
into two main bronchi, thus giving rise to
three lobes on the right and two on the left.
The lingula on the left is the middle lobe
equivalent; however, the left lung is smaller
than the right.
Normal Lung
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The right main stem bronchus is more
vertical and more directly in line with
the trachea than is the left.
Consequently, aspirated foreign
material, such as vomitus, blood, and
foreign bodies, tends to enter the right
lung rather than the left.
Normal Lung
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The main right and left bronchi branch
give rise to progressively smaller
airways.
Progressive branching of the bronchi
forms bronchioles, which are
distinguished from bronchi by the lack
of cartilage and submucosal glands
within their walls.
Normal Lung

Further branching of bronchioles leads
to the terminal bronchioles, which are
less than 2 mm in diameter. The part of
the lung distal to the terminal
bronchiole is called the acinus; it is
approximately spherical, with a
diameter of about 7 mm.
Normal Lung
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An acinus is composed of respiratory bronchioles ,
which give off several alveoli from their sides.
These bronchioles then proceed into the alveolar
ducts, which immediately branch into alveolar sacs,
the blind ends of the respiratory passages, whose
walls are formed entirely of alveoli, which are the site
of gas exchange.
The alveoli open into the ducts through large mouths.
All alveoli are open and have incomplete walls. A
cluster of three to five terminal bronchioles, each
with its appended acinus, is usually referred to as the
pulmonary lobule.
Normal Lung

The entire respiratory tree, including
the larynx, trachea, and bronchioles, is
lined by pseudostratified, tall, columnar,
ciliated epithelial cells, heavily admixed
in the cartilaginous airways with mucussecreting goblet cells- except for the
vocal cords, which are covered by
stratified squamous epithelium,
The microscopic structure of the
alveolar walls
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The capillary endothelium lining the
intertwining network of anastomosing
capillaries.
A basement membrane and surrounding
interstitial tissue separating the endothelial
cells from the alveolar lining epithelial cells.
In thin portions of the alveolar septum, the
basement membranes of epithelium and
endothelium are fused, whereas in thicker
portions, they are separated by an interstitial
space (pulmonary interstitium) .
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Alveolar epithelium, which contains a continuous layer
of two principal cell types:
flattened, platelike type I pneumocytes (or
membranous pneumocytes)
covering 95% of the alveolar surface and rounded
type II pneumocytes.
Type II cells are important for at least two reasons:
(1) They are the source of pulmonary surfactant,
contained in osmiophilic lamellar bodies seen with
electron microscopy, and (2) they are the main cell
type involved in the repair of alveolar epithelium
after destruction of type I cells.
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Alveolar macrophages, loosely attached to the
epithelial cells or lying free within the
alveolar spaces, derived from blood
monocytes and belonging to the mononuclear
phagocyte system. Often, they are filled with
carbon particles and other phagocytosed
materials.
The alveolar walls are not solid but are
perforated by numerous pores of Kohn, which
permit the passage of bacteria and exudate
between adjacent alveoli
Introduction
 Daily
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10,000 liters of air – filtered
 Nasopharyngeal flora (during sleep)
 Virulent organisms.
Pneumonia: Inflammation of lung.
Respiratory tract infections –
commonest in medical practice.
Enormous morbidity & mortality.
Etiology
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Decreased resistance - General/immune
Virulent infection - Lobar pneumonia
Defense Mechanisms
In the normal respiratory system there are
a number of important defense mechanisms
that protect the lung from infection. These
include:
 Reflex closure of the vocal cords
 Cough reflex
 Mucociliary clearance
 Macrophage activity and immune
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An increased risk of bacterial
infection is associated with impairment
of the defense mechanism, as in any of
these clinical situations:
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Loss of consciousness
Immunodeficiency state
Pulmonary edema
Neutropenia
Chronic airway obstruction
Viral infection.
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Exudate
The exudate in bacterial pneumonia is
typically composed of varying proportions of:
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edema fluid
red blood cells
leukocytes (principally neutrophils)
fibrin
The cellular exudate in acute bacterial
pneumonia is in the alveolar spaces and distal
bronchioles though in severe cases the major
airways may also be filled with purulent
secretion.
Types
 Viral
 Bacterial
 Mycoplasmal
 Fungal
The Pneumonia Syndromes
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Community-acquired
acute pneumonia
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Streptococcus pneumonia
Haemophilus influenza
Moraxella catarrhalis
Staphylococcus aureus
Legionella pneumophilia
Klebsiella
Pseudomonas
Community-acquired
atypical pneumonia
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Mycoplasma
Chlamydia
Legionella
Viruses (RSV,
parainfluenza & influenza,
adenovirus)
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Nosocomial pneumonia
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Aspiration pneumonia
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Anaerobic oral flora
Amniotic fluid
Gastric content
Chemicals
Chronic pneumonia
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Gram negative rods
Staphlyococcus aureus
Nocardia
Actinomyces
Granulomatous
Necrotizing pneumonia
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Anaerobic
Staphlyococcus aureus
Klebsiella
Streptococcus pyogens
Patterns of Pulmonary
infections
 Airway
– Bronchitis/Bronchiolitis,
Bronchiectasis
 Parenchyma
 Pneumonia
Bronchopneumonia
Lobar
pneumonia
 Lung abscess
 Tuberculosis
Routes of Infection
Several possible routes of infection of
the lung exist:
Aspiration of contaminated secretions-most common
 Inhalation of infected airborne droplets
 Bacteremia
 Direct extension of an acute inflammatory
process from an adjacent organ or
structure.

Etiopathogenesis
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Causes of bacterial pneumonia can be categorized as
extrinsic and intrinsic.
Extrinsic factors : infection with respiratory
pathogens. Exposure to pulmonary irritants or direct
pulmonary injury causes noninfectious pneumonitis.
 Infectious agents responsible for bacterial
pneumonias include S. pneumoniae and H. influenzae;
Klebsiella, Staphylococcus, and Legionella species;
and gram-negative organisms.
 Aspiration and inhalation of aerosols containing the
bacterial pathogen are the most common modes of
infection.
 Some bacteria, such as Staphylococcus species, may
spread to the lungs hematogenously.
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S. pneumoniae is the most common cause of bacterial
pneumonia.
Pneumonia from H influenzae often is associated with
debilitating conditions such as asthma, COPD, smoking,
and a compromised immune system.
K. pneumoniae may cause a severe necrotizing lobar
pneumonia in patients with chronic alcoholism, diabetes,
or COPD.
S. aureus pneumonia is observed in those who abuse
intravenous drugs.
 S. aureus generally occurs in hospitalized patients and
patients with prosthetic devices; it spreads
hematogenously to the lungs from contaminated local
sites. This pathogen also is an important cause of
pneumonia following infection with influenza A.
L. pneumophila infections occur either sporadically or as
local outbreaks.

Gram-negative pneumonias are
observed in individuals who are
immunocompromised or
hospitalized.
 Causative
organisms include
Escherichia coli and Pseudomonas,
Enterobacter, and Serratia species.
Residents of chronic care facilities
are at risk for gram-negative
pneumonia.

Intrinsic factors : related to the host's immune
response, the presence of comorbidities, and
other risk factors:
 Loss of protective reflexes allows aspiration
of oropharyngeal flora into the lung.
 Aspiration is facilitated by altered mental
status from intoxication, deranged
metabolic states, neurological causes (eg,
stroke), and endotracheal intubation.
 Local lung pathologies (eg, tumors, chronic
obstructive pulmonary disease [COPD],
bronchiectasis).
 Smoking impairs the host's defense to
infection by a variety of mechanisms.
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Aspiration pneumonia is observed in
individuals with altered sensorium (eg,
seizures, alcohol intoxication, drug
intoxication) or CNS impairment (eg,
stroke).
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The stomach or oropharyngeal contents are
aspirated.
Complications of Pneumonia
 Destruction of lung tissue from infection
(leading to bronchiectasis)
 Organization of the exudate
 Abscess formation
 Spread of the infection to the pleural cavity
(empyema)
 Sepsis & Pyemia
 Respiratory failure
 Acute respiratory distress syndrome
 Superinfection with gram-negative organisms
 Death
1. Pneumonia
1.1. Bronchopneumonia
1.2.
1.3.
Lobar pneumonia
Viral (Atypical)
pneumonia
1.1. Bronchopneumonia
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Staph, Strep, Pneumo & H. influenza
Bronchopneumonia is characterized by
focal areas of suppurative inflammation,
in a patchy distribution, involving one or
multiple lobes.
Usually bilateral
Lower lobes common
Complications:
Abscess
 Empyema
 Dissemination.
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The inflammatory exudate in each of
the foci of involvement typically
involves a small airway and surrounding
alveolar spaces.
Histologically
The relatively small areas of involvement
 Focal areas of suppurative inflammation in a
patchy distribution.
 Abscess formation.
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Bronchopneumonia
Patchy
consolidation –
not limited to
lobes
Bronchopneumonia
Bronchopneumonia
Bronchopneumonia: Abscess
formation
Bronchopneumonia
Bronchopneumonia
Bronchopneumonia - Abscess
formation
Bronchopneumonia - CT
1.2. Lobar Pneumonia
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Fibrinosuppurative consolidation – whole
lobe
Rare (due to antibiotic treatment)
~95% - Strep. pneumoniae types 1,3,7& 2
Four stages (Laennec,1838) :
 Congestion & edema (1 to 2 days)
 Red Hepatization (2-4 days )
 Gray Hepatization (4 to 8 days)
 Resolution (1 to 3 weeks).
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Congestion & Edema:
This stage is characterized histologically
by:
 vascular engorgement,
 intra-alveolar fluid,
 small numbers of neutrophils,
 often numerous bacteria.
 Grossly, the lung is heavy and
hyperemic.
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Red hepatization:
Vascular congestion persists,
 Extravasation of red cells into alveolar
spaces,
 Increased numbers of neutrophils and
fibrin.
 The filling of airspaces by the exudate
leads to a gross appearance of
solidification, or consolidation, of the
alveolar parenchyma.
 A dry, granular, dark-red lung surface
on gross appearance
 This appearance has been likened to
that of the liver, hence the term
"hepatization".
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Gray hepatization:
 As pneumonia progresses over 2-3
days, erythrocytes are lysed with
persistence of the neutrophils and
fibrin and, epithelial cells degenerate
 The alveoli still appear consolidated,
but grossly the color is paler and the
cut surface is drier.
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Resolution:
The exudate is digested by enzymatic
activity, and cleared by macrophages or
by cough mechanism.
 Dying pneumococci release a preformed
toxin, further contributing to this
damage.
 The pneumococci are opsonized by
leukocytes and begin to be cleared.
 Resolution results in the formation of
jellylike yellowish-colored exudates.
 Absorption of these exudates is
remarkably efficient, with little
organization or permanent scaring.
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Lobar
Pneumonia
Lobar Pneumonia – Gray hepatization
Strep. Pneumoniae Pneumonia
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Streptococcus pneumoniae produces few
toxins.
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It causes diseases by its capacity to
replicate in host tissues.
The presence of a capsule allows an
escape from phagocytosis, resulting in
an intense inflammatory response in
hosts who are immunologically naive.
Colonization of the oropharynx by
bacterial adherence to human
pharyngeal cells is the usual first step.
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The alternative pathway of the
complement is first activated.
Anticapsular antibodies are
effective in providing protection
against pneumococcal infection.
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They appear 5-8 days after the onset
of infection. By this time, fever usually
disappears in the absence of
treatment.
Natural immunity follows infections
as well as colonization.
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Conditions that predispose the patient to
pneumococcal infection
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Defective antibody formation
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Agammaglobulinemia and hypogammaglobulinemia,
multiple myeloma, chronic lymphocytic leukemia,
lymphoma, and HIV infection
Defective complement (C1 to C4)
 Defective splenic function
 Asplenia and splenectomy
 Chronic diseases
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Chronic obstructive pulmonary disease, cirrhosis of
the liver, and alcoholism
Acute viral respiratory infections
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Post–influenza virus
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Pneumonia:
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The absence of predisposing factors is rare
in pneumococcal pneumonia affecting
elderly children, teenagers, and adults
younger than 60 years.
Meningitis:
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Predisposing factors include head trauma,
cerebrospinal fluid leak, and respiratory
tract infection.
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Pneumonia:
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Complications
Pleural effusions
Abscess
Empyema.
Meningitis (if present)
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Cranial nerve palsies (III, VI, VII, VIII) usually
disappear within a few weeks.
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Vasculitis and cerebral infarction
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Approximately 10% of infants and children are left with
persistent unilateral or bilateral sensory hearing loss.
epilepsy, and mental retardation.
Obstructive hydrocephalus
Subdural empyema.
1.3. Atypical pneumonia
(Interstitial pneumonia)
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Primary atypical pneumonia denotes
the moderate amount of sputum,
no physical findings of consolidation,
moderate elevation of white cell count
lack of alveolar exudate
1.3. Atypical pneumonia
(Interstitial pneumonia)
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The etiologic agent in children:
Virus (62%)
 Bacteria (53%)
 Both viral and bacterial pathogens-mixed
infection (30%).
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The etiologic agent in adult:
Bacteria (40%)
 Virus (11%).
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Mycoplasma infections are common
among children and young adults. They
occur sporadically or local epidemics in
closed communities.
Viral pneumonia can vary from a mild
illness to a life-threatening disease with
severe hypoxemia.
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Adults frequently are infected with
both bacterial and viral pathogens;
therefore, differentiating viral
disease from bacterial disease may be
impossible.
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Patients with the greatest risk for
severe disease:
Immunocompromised patients,
 Chronic illnesses.
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Nosocomial pneumonias:
Adenovirus,
 Influenza A and B,
 Parainfluenza,
 RSV.
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Viruses are divided into categories depending
on whether the pneumonia they cause is a
primary manifestation or part of a
multisystem syndrome of disease.
Pneumonia as a primary manifestation
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influenza virus types A and B,
RSV,
adenovirus,
parainfluenza virus,
rhinovirus,
hantavirus,
CMV.
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Pneumonia as part of a multisystem
syndrome
Paramyxovirus species (measles),
 varicella-zoster virus,
 Epstein-Barr virus,
 CMV,
 herpes simplex virus
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Pathology
Bilateral/unilateral involvement,
Patchy lesions,
Inflammatory infiltration confined
within the walls, with:
Edema
 Mononuclear cells (lympho, histio, plasma)
 In severe cases:
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Diffuse alvolar damage
 Hyaline membranes)
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Respiratory syncytial virus (RSV) infection
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Manifests primarily as
bronchiolitis and/or viral
pneumonia,
Peak incidence of
occurrence is observed at
age 2-8 months.
Reinfection with RSV
occurs at all ages (limited
to the URT).
RSV bronchiolitis in the
first year of life is one of
the most important risk
factors for the
subsequent development
of asthma.
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Risk for severe RSV
infection:
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less than six weeks of age,
infants with a history of
prematurity,
those with congenital heart
disease, chronic lung
conditions or
immunodeficiency.
Others:
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lower socioeconomic status,
crowded living conditions,
exposure to passive
cigarette smoking
avoidance of breast
feeding.
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Respiratory viruses
damage the respiratory tract
 stimulate the host to release multiple
humoral factors,
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histamine, leukotriene C4, and virus-specific
immunoglobulin E in RSV infection and bradykinin,
interleukin-1, interleukin-6, and interleukin-8 in
rhinovirus infections.
RSV infections can also alter bacterial
colonization patterns, increase bacterial
adherence to respiratory epithelium,
reduce mucociliary clearance, and alter
bacterial phagocytosis by host cells.
Lung RSV Pneumonia
Influenza virus
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The most common cause of viral pneumonia in adults.
Three serotypes of influenza virus exist: A, B, and C.
 Influenza type A is the serotype most frequently
responsible for major epidemics and pandemics; it is
the most frequent cause of viral pneumonia in adults.
 Influenza type A can alter surface antigens and
infect livestock; perhaps, this ability accounts for
its ability to create a reservoir for infection and
cause epidemics in humans.
 Influenza type B cause illness, which usually is seen in
relatively closed populations such as boarding schools.
 Influenza type C is less common and occurs as sporadic
cases.
Parainfluenza virus
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Parainfluenza infection occurs early in
life and may cause pneumonia.
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Infection later in life is usually mild.
Four antigenically distinct serotypes of
the virus exist; however, types 1, 2, and
3 cause more severe disease than that
of type 4.
Parainfluenza viruses are second in
importance to only RSV in causing lower
respiratory tract disease in children and
pneumonia and bronchiolitis in infants
younger than 6 months.
Adenovirus
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Type 7 viruses can cause bronchiolitis and
pneumonia in infants.
Types 4 and 7 viruses are responsible for
outbreaks of respiratory disease in military
recruits.
Studies of atypical pneumonia in military
personnel have shown that adenovirus is the
etiology in as many as 40% of cases.
Severe adenovirus pneumonia may occur in
infants, immunocompromised patients, and
rarely, healthy adults.
Paramyxovirus
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Causing disease in unimmunized children
and adults.
Immunity to measles (rubeola) is
maintained throughout one's lifetime.
Pneumonia occurs in 5% of measles
cases, with death from measles in 1 per
1,000 patients.
Most deaths are due to pneumonia.
CMV
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An extremely important cause of pneumonia in
immunocompromised patients.
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Reactivation of latent infection is almost universal
in transplant recipients and individuals infected
with the human immunodeficiency virus.
Additionally, CMV infection is immunosuppressive
as well, causing further immunocompromise in
these patients.
The virus has been found in the cervix and in
human milk, semen, and blood products.
In cancer patients receiving allogenic bone
marrow transplants, CMV pneumonia has a
prevalence of 15% and a mortality rate of
85%.
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Varicella-zoster virus:
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Herpes simplex virus:
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In immunocompromised children/adults.
Pneumonia may develop from primary
infection or reactivation.
Epstein-Barr virus:
Pneumonia as a complication of
mononucleosis is very uncommon.
 The virus can cause pneumonia in the
absence of mononucleosis.

 Complications:
Respiratory failure
 Pulmonary fibrosis
 Noncardiogenic pulmonary edema
 Superimposed bacterial infection
 Adult respiratory distress syndrome
 Reye syndrome
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Severe Acute Respiratory Syndrome
SARS
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First appeared in 2002 in China
Coronavirus
After incubation period of 2-10 days patients
develop dry cough, malasie, myalgias, fever
and chills
10% die of disease no specific treatment
Can be detected by PCR or antibodies
The lungs of the patients show diffuse
alveolar damage and multinucleated giant cells
Chronic Pneumonia
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Chronic pneumonia is most often a
localized lesion in the immunocompetent
patient, with or without regional lymph
node involvement.
There is granulomatous infection, which
may be due to
-bacteria M. Tuberculosis
-fungi H.capsulatum, Blastomycosis,
coccidioides
Chronic Pneumonia
Fungal pneumonia
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Endemic fungal pathogens (eg, Histoplasma
capsulatum, Coccidioides immitis, Blastomyces
dermatitidis, Paracoccidioides brasiliensis) cause
infection in both healthy and
immunocompromised host.
Opportunistic fungal organisms (eg, Candida
species, Aspergillus species, Mucor species,
Cryptococcus neoformans) tend to cause
pneumonia in patients with congenital or acquired
defects in their host defenses.
Etiology
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Workers or farmers with heavy exposure to bird, bat, or
rodent droppings and other animal excreta.
C. immitis, because of its virulence, also is a threat among
laboratory personnel working with this fungus.
Conditions that predispose patients to any of the
opportunistic fungal pathogens are as follows:
 Acute leukemia or lymphoma during myeloablative
chemotherapy
 Bone marrow transplantation
 Solid organ transplantation on immunosuppressive
treatment
 Prolonged corticosteroid therapy
 AIDS
 Prolonged neutropenia from various causes
 Congenital immune deficiency syndromes.
Histologic Findings:
Caseating or necrotizing granulomas
with intracellular organisms inside
macrophages (eg, H capsulatum, C
immitis)
 Fungal hyphae in Aspergillus and Mucor
species
 Intracellular yeast organisms in
Candida species.
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Complications:
 Blood vessel invasion (Dissemination and
sepsis)
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Pulmonary hemoptysis, infarction, myocardial
infarction, cerebral emboli, cerebral infarction, or
blindness.
Dissemimnation to other sites (brain, meninges,
skin, liver, spleen, kidneys, adrenals, heart, eyes).
Other complications
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Bronchopleural or tracheoesophageal fistulas
Chronic pulmonary symptoms
Mediastinal fibrosis (histoplasmosis)
Broncholithiasis (histoplasmosis)
Pericarditis and other rheumatologic symptoms.
Tuberculosis
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Pulmonary infection with Mycobacterium tuberculosis
is acquired as a result of inhaling the tuberculosis
bacillus suspended in the aerosolized sputum coughed
up by an infected individual with "open" tuberculosis.
Two phases of this disease occur:
 Primary tuberculosis
 By definition, this infection occurs in an
individual not previously exposed and sensitized
to tubercle bacilli.
 Secondary (reactivation) tuberculosis
 By definition, this is tuberculosis which becomes
clinically evident in an individual already
sensitized to the tubercle bacillus.
Primary Tuberculosis

The sequence of events in primary infection
typically involves:
 inhalation of infected airborne droplet
 particle size (approximately 3 microns) favors
deep inhalation and retention of the organism
 the bacilli tend to locate in the subpleural
midzone of lung
 the earliest radiographic appearance is an illdefined localized "atypical" pneumonia
 after a brief acute inflammatory reaction
associated with a neutrophilic response, the
bacilli invoke granuloma formation.
 By 2 to 8 weeks, the pneumonic focus becomes
a more defined radiographic opaque single
spheroidal lesion  Ghon focus.
In Non Immunized individuals (Children)
 Primary Tuberculosis:
Self Limited disease
 Ghons complex or Primary complex.
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Primary Progressive TB
10% of adults, Immunosuppressed
individuals
 Common in malnourished children
 Miliary TB and Meningitis.
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A single lesion (the Ghon focus) occurs just
under the pleura in the midportion (in the
lower part of the upper lobes -- the bestventilated area) of one lung.
An active Ghon focus is a 1-1.5 cm area of
gray-white inflammatory consolidation
circumscribed from the surrounding lung
tissue.
The bacilli (either free or within phagocytes)
find their way to the regional
(tracheobronchial) lymph nodes, and in a few
weeks, granulomas have walled off the bacilli
in both locations.
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The combination of lesions in the lung
and lymph node involvement is called the
Ghon complex.
Healed complexes are small and may be
hard to detect by either pathologic or
radiologic studies.
Viable bacilli remain in the Ghon
focus/complex for life.
Entrance into the lymphatics permits
multiorgan dissemination.
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The minimal lesion in the apex consists of a
1-3 cm focal area of caseous consolidation
 remains localized/progress slowly 
rapid caseation a fibrotic wall surrounds
the lesion.
Microscopy:
Tubercule formation (by the epitheloid
cells)
Langhans’ giant cells
Caseation (caseous necrosis)
Lymphocytic infiltration
Fibrosis.
Course of the disease


The more usual course is the fibrosis
and calcification of the Ghon complex;
tubercle bacilli lie dormant even with
fibrosis and calcification of the
granulomas.
The latent phase may persist
throughout life, the only index of
infection being a positive PPD (purified
protein derivative) reaction and the
presence of the obsolete fibrocalcific
Ghon complex.

Subsequent course varies:
occasionally because of the virulence of the
organism or poor host resistance, infection
spreads either via airspaces, leading to a
tuberculous bronchopneumonia, or
 Via the bloodstream, leading to formation
of myriads of small granulomas in one or
several organs (miliary tuberculosis).

Secondary Tuberculosis

Secondary/Reactive tuberculosis
Reactivation of dormant bacilli is
considered the most common source of
secondary tuberculosis, but reinfection
from an outside source is believed to occur
in some cases.
 The cause of reactivation is presumed to
be a decline in host immunocompetence.
 There is increased risk for reactivation in
patients with AIDS, alcoholism, diabetes,
certain malignancies, or undergoing steroid
or radiation therapy.







Post Primary in immunized individuals
Reactivation or Reinfection
Apical lobes or upper part of lower
lobes
Caseation, cavity - soft granuloma
Pulmonary or extra-pulmonary
Local or systemic/miliary



Secondary TB arises in a previously sensitized
individual, and occurs when :
 bacilli escape the original Ghon focus
(endogenous) or,
 more bacilli enter the body from outside
(exogenous).
The infection usually reappears in the apical or
posterior segments of one or both upper lobes
(Simon's foci), and progress slowly.
Secondary tuberculosis
 active TB,
 postprimary tuberculosis,
 adult tuberculosis,
 reinfection tuberculosis,
 cavitary tuberculosis



The location of granulomas is typically in
the apices of the lungs. This is probably
due to relatively high tissue oxygen levels
in this portion of the lung. The tubercle
bacillus is aerophilic.
The fibrotic reaction tends to confine
the typical lesion, but concurrently there
is an increased tendency to tissue
destruction and cavitation.
Cavitation favors proliferation of
organism and spread to contacts.


Dissemination:
 Entrance into the lymphatics permits multiorgan
dissemination.
 "Miliary" tuberculosis is characterized by
numerous minute granulomas in lung and/or
extrapulmonary sites.
Hypersensitivity enhances resistance and induces a
more prompt response by activated macrophages
and fibroblasts.
 It is the variable spectrum of the interaction of
hypersensitivity and fibrotic reaction which
determines the natural course of the disease,
which ranges from cure through continuous
progression, or multiple exacerbations to death.
-tubercle
formation (by the
epitheloid cells)
-Langhans’ giant
cells
-caseation
-lymphocytic
infiltration
-fibrosis.
Other Types of
Pneumonia
Congenital pneumonia



Pneumonitis that presents within the first 24
hours after birth.
Newborn infants typically have sterile
respiratory mucosa at birth, with subsequent
uncontested colonization by microorganisms
from the mother or environment.
Accelerated access to distal respiratory
structures and bypass of much of the ciliary
escalator occur in infants who require
endotracheal intubation.

In these infants, increased physical disruption of
epithelial and mucous barriers also occurs. In
addition, therapeutic exposure to high oxygen
concentrations and airway pressures interferes
with ciliary function and mucosal integrity.




Pneumonia that becomes clinically
evident within 24 hours of birth may
originate at 3 different times. Overlap
often exists among the 3 types, and
assigning a particular pneumonic episode
to one of these categories may be
difficult. The 3 categories of congenital
pneumonia are
(1) true congenital pneumonia,
(2) intrapartum pneumonia,
(3) postnatal pneumonia.


True congenital pneumonia is already established at
birth.
Transmission of congenital pneumonia usually occurs
via 1 of 3 routes:



1. Hematogenous transmission: If the mother has a
bloodstream infection, the microorganism can readily cross
the few cell layers that separate the maternal from the
fetal circulation at the villous pools of the placenta.
2. Ascending transmission: Ascending infection from the
birth canal and aspiration of infected or inflamed amniotic
fluid have significant common features.
3. Transmission via aspiration: Most bacterial infections
produce clinical signs of infection in the mother, but
infections may not be evident if the membranes rupture
shortly after inoculation, similar to drainage of an abscess.

Intrapartum pneumonia is acquired during passage
through the birth canal.
 Intrapartum pneumonia may be acquired via
hematogenous or ascending transmission, or it may
result from aspiration of infected or contaminated
maternal fluids or from mechanical or ischemic
disruption of a mucosal surface that has been freshly
colonized with a maternal organism of appropriate
invasive potential and virulence.
 Infants who aspirate proinflammatory foreign
material, such as meconium or blood, may manifest
pulmonary signs immediately after or very shortly
after birth.

Postnatal pneumonia in the first 24 hours of life
originates after the infant has left the birth canal.
 Colonization of a mucoepithelial surface with an
appropriate pathogen from a maternal or
environmental source and subsequent
disruption allows the organism to enter the
bloodstream, lymphatics, or deep parenchymal
structures.
 Enteral feedings may result in aspiration
events of significant inflammatory potential.
 Indwelling
feeding tubes may further
predispose infants to gastroesophageal
reflux and other aspiration events.
These infants are often relatively
asymptomatic at birth or manifest
noninflammatory pulmonary disease
consistent with gestational age, but
they develop signs that progress well
after 24 hours.

Agents of chronic congenital infection may
cause pneumonia in the first 24 hours of
life;


Cytomegalovirus, Treponema pallidum,
Toxoplasma gondii, and others,
Chlamydia organisms presumably are
transmitted at birth during passage
through an infected birth canal, although
most infants are asymptomatic during the
first 24 hours and develop pneumonia only
after the first 2 weeks of life.
Pathology:
 Macroscopy
The lung may have diffuse, multifocal, or very
localized involvement with visibly increased
density and decreased aeration.
 Frankly hemorrhagic areas and petechiae on
pleural and intraparenchymal surfaces are
common.
 Airway and intraparenchymal secretions may
range from thin and watery to serosanguinous
to frankly purulent and frequently are
accompanied by small-to-moderate pleural
effusions that display variable concentrations
of inflammatory cells, protein, and glucose.


Microscopy
Mononuclear cells (macrophages, natural killer
cells, small lymphocytes) usually are noted
early,
 Granulocytes (eosinophils, neutrophils) typically
become more prominent later.


If systemic neutropenia is present, the number of
inflammatory cells may be reduced.
Microorganisms.
 Alveoli may be atelectatic from surfactant
destruction or dysfunction, partially expanded
with proteinaceous debris (often resembling
hyaline membranes), or hyperexpanded
secondary to partial airway obstruction from




Hemorrhage in the alveoli and in distal
airways is frequent. Vascular congestion is
common; vasculitis and perivascular
hemorrhage are seen less frequently.
Inflammatory changes in interstitial tissues
are less common in newborns than in older
individuals.
Examination of the placenta may be useful.

An unusually large placenta with a thick
umbilical cord or necrotizing funisitis is
suggestive of congenital syphilis, with an
increased risk of congenital pneumonia alba.
Bronchiolitis Obliterans
Organizing Pneumonia


Characterized by the presence of
granulation tissue in the distal air
spaces.
When associated with granulation
tissue in the bronchiolar lumen,
organizing pneumonia is qualified by the
term bronchiolitis obliterans (BO).

Hence, the term bronchiolitis obliterans
organizing pneumonia is used.

Organizing pneumonia may be classified
according to whether
(1) its cause is determined,
 (2) its cause is undetermined but
occurring in a specific and relevant
context, or
 (3) it is Cryptogenic (idiopathic) organizing
pneumonia (COP).


Cryptogenic organizing pneumonia is a
clinicopathologic syndrome characterized by
rapid resolution with corticosteroids but
frequent relapses when treatment is tapered
or stopped.
Pathophysiology:
 Approximately one half of cases of Bronchiolitis
obliterans organizing pneumonia (BOOP) are
idiopathic.
 A variety of conditions are associated with
BOOP as follows:


Radiation therapy: In patients treated with
radiation therapy for small cell bronchogenic
carcinoma or breast cancer, BOOP may affect the
ipsilateral or contralateral lung.
Infections: Infection may be caused by Coxiella
burnetii, Pseudomonas aeruginosa,Mycoplasma
species, human herpesvirus 7 (after lung
transplantation), Pneumocystis carinii in patients
(after liver transplantation), influenza A virus,
measles virus, parvovirus B19, HIV, Chlamydia
species, Plasmodium vivax, or Plasmodium malariae.

Drugs and toxins: BOOP is associated with
exposure to minocycline; gold;
cephalosporin; acebutolol; sulfasalazine;
mesalazine; bucillamine; interferon beta-1a;
nitrofurantoin; amiodarone; ticlopidine;
carbamazepine; phenytoin; sotalol; rapid
intravenous cyclophosphamide pulse
therapy; a combination of cytosine
arabinoside, anthracyclines, and massive Ltryptophan ingestion, Sauropus androgynus
vegetable poisoning, exposure to paint
aerosols in textile workers, nylon flock
workers, silo-filler's disease, free-base
cocaine use, and smoke inhalation.

Associated pathologies

Connective tissue disease


Rheumatoid arthritis, Sjögren syndrome, ankylosing spondylitis,
polymyositis-dermatomyositis, cutaneous vasculitis, Behçet
disease, Wegener granulomatosis, ulcerative colitis, Crohn
disease, systemic sclerosis, systemic lupus erythematosus,
systemic lupus erythematosus with antiphospholipid syndrome,
primary biliary cirrhosis, and thyroiditis
Immunosuppressed states

Hematopoietic stem cell transplantation (HSCT), graft versus
host disease of the liver after allogenic bone marrow
transplantation, renal transplantation, coronary artery bypass
graft surgery, kidney transplantation with Fabry disease, T-cell
leukemia, primary non-Hodgkin lymphoma, malignancies in
children, myelodysplastic syndrome, recent surgery, severe
pneumonia, adult respiratory distress syndrome, and acquired
immune deficiency syndrome
Pneumonia in
Immunocompromised
patients


Pneumonia in the immunocompromised
host involves infection and inflammation
of the lower respiratory tract.
It most commonly is seen in patients
infected with a human immunodeficiency
virus (HIV),
 myelosuppressive chemotherapy,
 organ transplantation,
 traditional immunosuppressive illness


Hodgkin disease.
Etiology









P carinii (in HIV-seropositive individuals)
Gram-negative bacilli
Staphylococcus and Aspergillus species
(predominant in patients with cancer)
Fungi
Viruses (particularly CMV)
P. carinii initially with bone marrow transplantation
and Streptococcus pneumoniae more common later
Nosocomial bacteria initially in renal
transplantation, with opportunistic pathogens more
common later (eg, cytomegalovirus, P. carinii;
Legionella, Aspergillus, Nocardia species)
Mycobacterium avium-intracellulare (AIDS)
Gram-negative bacilli initially with heart or liver
transplantation.
Complications:
Pneumothorax
 Hypoglycemia (may occur with pentamidine)
 Respiratory failure
 Adult respiratory distress syndrome
 Superinfection
 Pleural effusion
 Empyema
 Death.

...in Immunocompromised
patientsAspergillus and fungus ball
Aspergillosis
Chemical Pneumonies

Many substances can cause chemical
pneumonia, including liquids, gases,
and small particles, such as dust or
fumes, also called particulate
matter. Some chemicals only harm
the lungs; however, some toxic
materials affect other organs in
addition to the lungs and can result
in serious organ damage or death.

Chemical pneumonia includes:
Insecticides
 Pool cleaning chemicals
 Gasoline fumes
 Toxic gas (phosgene, chlorine)
 Aspirated/Inhalated chemicals


Complications of Chemical inhalation:
Cyanosis
 Pneumonia
 Respiratory failure.

Aspiration Pneumonia

Aspiration (the act of taking foreign
material into the lungs), can cause a
number of syndromes determined by
the quantity and nature of the aspirated
material, the frequency of aspiration,
and the host factors that predispose
the patient to aspiration and modify the
response.

Three types of material cause 3 different
pneumonic syndromes.



Aspiration of gastric acid causes chemical
pneumonia (Mendelson syndrome).
Aspiration of bacteria from oral and pharyngeal
areas causes bacterial pneumonia.
Inhalation/aspiration of chemicals





Aspiration of oil, eg, mineral oil or vegetable oil, causes
exogenous lipoid pneumonia, a rare form of pneumonia.
Organic dusts (hypersensitivity pneumonitis)
Inorganic particulates (silica, asbestos, talc, zinc)
Chemical fumes (sulfuric acid, hydrochloric acid, methyl
isocyanate)
Gases (oxygen, chlorine, nitrogen dioxide [silo-filler
disease], ammonia, CO).
Mendelson syndrome
 The parenchymal inflammatory
reaction caused by a large volume of
gastric contents independent of
infection.
 If the pH of the aspirated fluid is
less than 2.5, it has a greater
potential for causing chemical
pneumonia.
 The initial chemical burn is followed
by an inflammatory cellular reaction
fueled by the release of potent
cytokines (tumor necrosis factor–a
Bacterial pneumonia




Nosocomial.
The major pathogens involved are hospitalacquired flora through oropharyngeal
colonization (eg, enteric gram-negative bacteria,
staphylococci).
In anaerobic pneumonia, the pathogenesis is
related to the large volume of aspirated
anaerobes (eg, as in persons with periodontal
disease) and to host factors (eg, as in alcoholism)
that suppress cough, mucociliary clearance, and
phagocytic efficiency.
Colonization of gram-negative organisms in the
oropharynx, sedation, and intubation of the
patient's airways are important pathogenetic
factors in nosocomial pneumonia.
Risk factors

Conditions associated with
altered or reduced
consciousness







Alcoholism
Drug overdose
Seizures
Stroke
Head trauma
General anesthesia












Dysphagia
Esophageal strictures
Esophageal neoplasm
Esophageal diverticula
Tracheoesophageal fistula
Gastroesophageal reflux
disease





Multiple sclerosis
Dementia
Parkinson disease
Myasthenia gravis
Pseudobulbar palsy
Mechanical conditions

Esophageal conditions

Neurologic disorders
Nasogastric tube
Endotracheal intubation
Tracheostomy
Upper gastrointestinal endoscopy
Bronchoscopy
Other types of conditions




Protracted vomiting
General deconditioning and debility
Prolonged recumbency
Amniotic material
Eosinophilic pneumonia


Characterized by pulmonary eosinophilia and
infiltrates,
 with or without increased peripheral eosinophils in
the blood.
Causes:
 Primary Eosinophilic pneumonias are idiopathic and
are not related to drugs, medications, or systemic
diseases such as vasculitis.
 Secondary Eosinophilic pneumonias are induced by
 Parasites (eg, Ascaris lumbricoides,
Strongyloides stercoralis),
 Medications (eg, amiodarone, nitrofurantoin).

Histologic Findings
Eosinophils with edema in alveolar spaces
and bronchioles are observed.
 Additional cells are nonspecific and can
include monocytes, histiocytes, and
polymorphonuclear leukocytes or
neutrophils (PMN).

2. Lung Abscess
Lung Abscess



Focal suppuration with necrosis of lung
tissue
Strep, Staph & Gram negative & anaerobes
Mechanism:






Aspiration of infected material
Post pneumonic
Septic embolism
Neoplasms
Direct trauma
Spread from adjacent structures.



Abscesses may occur in any location in the
lung; they may be single or multiple.
Abscesses due to aspiration occur most
commonly in the right lung (because of
the more vertical course of the right main
stem bronchus) and are usually single.
Morphologically an abscess is a cavity
filled with suppurative debris.


If communication exists with an airway, the
exudate may drain, leading to air in the cavity,
and an air-fluid level on chest x-ray.
In chronic abscesses, there may be
peripheral fibroblastic proliferation
resulting in a fibrous wall.

Complications:
Empyema
 Systemic spread (pyemia/pyemic
abscesses)
 Septicemia.

Lung Abscess
Lung Abscess
Chronic Lung Abscess
Fungal Abscess: Candida albicans
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