PATHOLOGY OF LUNG INFECTIONS

BACTERIAL PNEUMONIA
Bacterial pneumonia is caused by bacterial invasion of the lung parenchyma
exudative solidification (consolidation) of the pulmonary tissue.

Pathogenesis of pneumonias
Pneumonia can result whenever the defense mechanisms are impaired or the resistance of the
host in general is lowered.

Factors that interfere with the defense mechanisms:

1. factors that interfere with the clearing mechanisms
Loss of the cough reflex, as a result of coma, anesthesia, neuromuscular disorders,
drugs, chest pain aspiration.
Injury to the mucociliary apparatus: tobacco smoke, inhalation of hot or corrosive
gases, viral diseases genetic disturbances e.g. immotile cilia syndrome.
Interference with the phagocytic action of alveolar macrophages: alcohol, tobacco
smoke, anoxia or oxygen intoxication.

2. pulmonary congestion and edema
3. accumulation of secretions (e.g. cystic fibrosis and bronchitis)

Factors that affect the resistance of the host:
chronic diseases
immunologic deficiency
treatment with immunosuppressive agents
leukopenia
unusually virulent infections

Features of pneumonia induced by bacteria
1. Main features: alveolar inflammation, protein rich exudate, accumulation of PNGs
later macrophages in the alveoli.

2. Main types:
bronchopneumonia
lobar pneumonia

Etiology of pneumonias

bronchopneumonia: the common agents are staphylococci, streptococci, pneumococci,
haemophilus influenzae, pseudomonas aeruginosa, and the coliform bacteria
lobaris pneumonia: 90% is due to streptococcus pneumoniae

Features of bronchopneumonia

usually in infancy and old age
usually secondary to pre-existing disease


Gross pathology:
patchy consolidation
frequently bilateral and basal
lesions are 3-4 cm in diameter, breakable, slightly elevated from the cut surface, dry,
granular, gray-red to yellow
Photo: Bronchopneumonia: gray-red patchy lesions, slightly elevated from the cut surface.

Histology:
suppurative, neutrophil-rich exudate fills the lumen of bronchi, bronchioles and
adjacent alveolar spaces
Photo: Purulent bronchiolitis: exudate, rich in neutrophil granulocytes fills the lumen of the
bronchiole.
Photo: Bronchopneumonia: exudate, rich in neutrophil granulocytes fills the lumen of the
alveoles focally.


Features of lobar pneumonia

affects large part of or an entire lobe
90% is due to streptococcus pneumoniae
fibrinoso-suppurative consolidation is seen
It is associated with fibrinous pleuritis
relatively uncommon in infancy and childhood
affects males more than females
cough and fever with purulent or rusty sputum

Morphology

Stages of lobar pneumonia:
1. Congestion: the affected lobe is heavy and red: LM:vascular engorgement, intraalveolar
fluid, few neutrophils, bacteria.
2. Red hepatization: red, airless lobe, with liver-like consistency. LM: vascular
engorgement, the alveolar spaces are filled RBCs, neutrophils and fibrin.
3. Gray hepatization: the lobe is grayish-brown and the cut surfaces are dry. LM:
disintegration of RBCs, fibrinosopurulent exudate in the alveoli.
4. Yellow hepatization: the gross appearance of the lobe is yellow. LM: high numbers of
foamy, desintegrating macrophages.
5. Resolution: the exudate undergoes progressive enzymatic digestion to produce granular,
semifluid debris that is resorbed, ingested by macrophages, or coughed up.

The average duration of the three hepatizations is two days each.

Photo: Lobar pneumonia, red hepatization. The whole lobe is red, airless, with liver-like
consistency.
Photo: Lobar pneumonia, fibrinous pleuritis. Gray-red fibrin on the pleural surface.
Photo: Lobar pneumonia, gray hepatization. The whole lobe is grayish and the cut surface is
dry.



Clinical course of pneumonias
Major symptoms: malaise, fever, and cough productive sputum.
When pleuritis is present: pleuritic pain and pleural friction rub.
The identification of the organisms and the determination of its antibiotic sensitivity
are the keys to appropriate therapy.
Fewer than 10% of hospitalized cases of pneumonia die, death may be attributed either
to a complication or to some predisposing disease.

VIRAL AND MYCOPLASMAL PNEUMONIA
(PRIMARY ATYPICAL PNEUMONIA - PAP)
It is atypical because there is a lack of alveolar exudates, the inflammation involves
the interstitium. Better term: interstitial pneumonitis.
Causes:
Mycoplasma pneumoniae (commonest)
Viruses:
Influenza virus types A and B
Respiratory syncytial viruses
Adenovirus
Rhinoviruses
Rubella virus
Varicella virus
Chlamydia (psittacosis)
Coxiella burnetti (Q fever)

Morphology of PAP

1. patchy or lobar areas of congestion, without consolidation
2. mononuclear inflammatory cell infiltrate, lymphocytes in the widened, edematous alveolar
walls (interstitial pneumonitis)
3. formation of hyaline membranes
4. frequent superimposed bacterial infection
5. characteristic cytopathic changes are seen with some viruses

Clinical course of PAP

extremely varied
fever, headache, and muscle aches
sporadic is usually mild with low mortality rate, below 1%
in viral influenza epidemics greater mortality is often due to fulminating pneumonia
with pulmonary haemorrhage and to secondary bacterial infection

Photo: Hemorrhagic tracheitis, influenza. Hyperaemic mucosa with hemorrhage.
Photo: Rs virus pneumonia in an infant, (influenza sy.). The lung is heavy and red.
Photo: Pneumonia, influenza. Interstitial round cell infiltrate, alveoli are lined by
homogenous eosinophil material, hyaline membranes.






TUBERCULOSIS (TBC)

Etiology of tuberculosis
Mycobacteria are aerobic, non-spore-forming, nonmotile bacilli. Their waxy coat is
responsible for the characteristic acid fast staining properties.
M tuberculosis(M tbc) hominis is transmitted by inhalation of infective droplets
coughed into the air by a tuberculosis patient.
M bovis is transmitted by milk from diseased cows and first produces intestinal or
tonsillar lesions.
M avium and M intracellulare (MAI), two closely related species have no virulence in
normal hosts, but cause disseminated infections in 15 to 25% of patients with AIDS.

Pathogenesis of tuberculosis
At initial infection with M tbc nonspecific inflammatory response ensues, resembling
the reaction to any form of bacterial invasion.
In 2 to 4 weeks after initial infection delayed hypersensitivity (type IV) develops to
the tubercle bacillus, that controls 95% of infections.

Tissue reactions to M. tbc

High resistance: productive (proliferative) lesions specific caseating epitheloid cell
granuloma i.e. tubercle formation
Low resistance: exudative lesions

Productive tuberculosis: tubercle formation
Components of tubercle:
central caseation: total tissue necrosis containing nuclear debris only
caseation is surrounded by modified macrophages, epithelioid cells
amongst the epithelioid cells: Langhans type giant cells, their nuclei are arranged at
the peripheri of cytoplasm in a horseshoe pattern
outermost layer: lymphocytes, fibroblasts, in time: scarring
number of M. tbc: low

Photo: Tubercle in lung. Central caseation, Langhans type giant cells (arrows).
Photo: Langhans cell. Nuclei are arranged in a horseshoe pattern at the periphery of the
cytoplasm.
Photo: Acid fast mycobacteria in caseous pneumonia.

Pathogenesis of tuberculosis
The pattern of host response depends on whether the infection represents a primary first
exposure to the organism or a secondary reaction in an already sensitized host.

Morphology of primary tuberculosis

Ranke-Ghon primary complex in the lung
subpleural focus (upper part of the lower lobe, buttom part of the upper lobe)
lymphangitis
hilar lymphadenitis
Photo: Morphology of primary tuberculosis. Ranke-Ghon primary complex.

Primary tuberculosis, outcome
The course and fate of this initial infection are variable, but in most patients are
asymptomatic and in most cases it heals.
The ultimate residuum of the primary infection is a calcified scar in the lung and in the
hilar lymph node.
Exceptionally primary infection may be followed by miliary tuberculosis.

Secondary tuberculosis
Foci of tuberculosis may reactivate, especially when the immunological resistance
decreases, e.g.
during puberty,
pregnancy
old age or
debilitating disease.
The resulting secondary tuberculosis is typically confined to one system only and
prefers to spread via preformed canaliculi (bronchi, ureter etc.).

Secondary pulmonary tuberculosis
In the lungs progressive pulmonary tuberculosis starts from the Simons foci, which are uni-
or bilateral apical lesions.
Photo: Simons focus: bilateral caseating tuberculotic foci in the upper lobes.

Secondary pulmonary tuberculosis
Possible clinicopathological consequences:
cavitary fibrocaseous tuberculosis,
tuberculous pneumonia (exudative lesion)
acinary, acinonodular or nodular tuberculosis (productive lesion)
and may be accompanied by miliary tuberculosis.

Cavity (caverna) in secondary tuberculosis
Expanding caseous necrosis affects the the wall of bronchi as well.
By erosion into a bronchus, drainage of the caseous debris results in cavity formation.
M tuberculosis can be transmitted by inhalation of infective droplets coughed into the
air by such patient.
Multiplication of M tbc is favoured by the increased oxygen tension.
The cavities are lined by caseous material and granulomatous tissue and are walled off
by scar tissue.
Photo: Apical lung cavernas in tuberculosis, drained by bronchus. Caseous necrosis affects
the the wall of bronchi, drainage of the caseous debris results in cavity (caverna) formation.


Miliary tuberculosis
Massive lymphohematogenous dissemination may give rise to miliary tuberculosis,
typically in people suffering from other debilitating disease. (milium [Latin] = millet)
Miliary tbc may be associated with primary tuberculosis, and not uncommon in the
elderly
accompanied to secondary tuberculosis.
Most bacilli are filtered out by the alveolar capillary bed, therefore the infective
material may not reach the systemic circulation, thus the miliary tuberculosis may be
restricted to the lung.

Systemic circulation is loaded with high number of M tbc. Favoured targets for
military seeding:
bone marrow,
liver,
spleen,
retina,
kidneys,
adrenals,
testes,
fallopian tube, etc.
The lesions are usually millet-sized distinct, yellow-white foci, showing the typical
microscopical features of tuberculous caseating granuloma.
Photo: Miliary tuberculosis in lung. Cut surface of formaldehyde fixed specimen:
numerous small gray-white granulomas n the lung.
Photo: Miliary tuberculosis: Numerous small caseous granulomas in the lung.




CHRONIC INTERSTITIAL LUNG DISEASES
clinical:
chronic restrictive lung disease
dyspnoe
decreased lung volume
decreased lung compliance

radilogy: diffuse infiltrates

pathology:
involves the alveolar interstitium
chronic round cell inflammation
lymphocyte, plasma cell, macrophages
than interstitial fibrosis may develop
consequence:
diffuse massive fibrosis
pulmonary hypertension
chr cor pulmonale


pathogenesis

initial event: epithelial or endothelial injury by inhaled or blood-borne toxins, agents
early acute: alveolitis with activated inflammatory cells, release of injurious (oxidant,
cytokines) and fibrogenic (PDGF, FGF) factors
late stages: progress to interstitial fibrosis


Chronic interstitial lung diseases

1. pneumoconiosis
2. idiopathic pulmonary fibrosis: Hamman-Rich syndrome
3. smokers pneumonitis
4. diffuse alveolar hemorrhage syndrome
5. bronchiolitis obliterans, organizing pneumonia
6. hypersensitivity pneumonitis
7. complications of therapies
8. Boeck sarcoidosis


1. Pneumoconiosis
lung injury caused by inhaled mineral or organic dusts, fumes

factors determining the health effect:
amount of dust retained
size and shape of particles, 1-5 micrometer is
pathogenic
physicochemical properties
lung injury caused by inhaled mineral or organic dusts, fumes

macrophages following phagocytosis release of enzymes, toxic free radicals +
fibrogenic cytokines and growth factors

consequence: tissue injury, interstitial fibrosis, chronic cor pulmonale


1.1 coal workers pneumoconiosis (CWP)
anthracosis
simple CWP
complicated CWP
1.2 silicosis
1.3 asbestosis


1.1 Coal workers pneumoconiosis (CWP)
A. anthracosis: small, harmless coal dust laden macrophages along lymphatics
B. simple CWP
gross: black coal macules in the upper lobes
histology: coal dust laden macrophages and
interstitial fibrosis around respiratory bronchioles
C. complicated: CWPlarge black scars in the upper lobes
dense collagen with pigment accumulation
Photo: Anthracosis. Coal dust laden macrophages outline the lymphatic chanels n black.
Photo: Anthracosis. Black coal dust laden macrophages.


consequence: depends on duration and magnitude of exposure
progressive massive fibrosis
pulmonary hypertension
chr cor pulmonale

1.2 Silicosis
chr nodular dense pulmonary fibrosis
occupational disease, quartz, metal grinding, ceramics, sandblasting
crystalline form: fibrogenic and carcinogenic
toxic on macrophages


1.2 Silicosis
gross: small fibrotic nodules, dense scars

histology: whorls of acellular collagen with birefringent silica particles under polarized
light, focal dystrophic calcification
Photo: Silicosis, gross: small fibrotic nodules, dense scars.
Photo: Silicosis, histology: whorls of acellular collagen with birefringent silica particles
under polarized light, focal dystrophic calcification.

1.3 Asbestosis
Asbestos is a family of fibrous silicates.
fiber types:
curled, flexible serpentines
pathogenic! straight, stiff amphiboles

pathomechanism: activated macrophages + direct tissue injury
asbestos body:
golden brown fusiform or beaded rods
asbestos fibers + iron containing proteinaceous material

Photo: Asbestos body: golden brown fusiform rod


injuries caused by asbestos:
1. pulmonary fibrosis
2. pleural effusions and adhesions
3. dense fibrocalcific plaques on the pleura and diaphragm
4. increase the risk of bronchogenic carcinoma, mesothelioma and laryngeal carcinoma


2. Idiopathic pulmonary fibrosis (IPF): Hamman-Rich syndrome

progressive pulmonary interstitial fibrosis of unknown cause
two thirds of patients are older than 60 yrs
more common in man
suspected that immune mechanisms are involved tissues
progression to pulmonary hypertension, chr cor pulmonale, cardiac failure
increased association of lung cancer with IPF (10%)


stages:
1. alveolitis, injury of type I pneumocytes, hyaline membrane formation + interstitial
pneumonitis with mononuclear cell infiltrate
2. patchy interstitial fibrosis, proliferation of type II pneumocytes, and fibroblasts
3. end stage: honeycomb lung, dense interstitial fibrosis with cystic air-spaces lined
by type II pneumocytes

Photo: Idiopathic pulmonary fibrosis:Hamman-Rich syndrome. The wall of alveoli is lined
by type II pneumocytes cuboid in shape.

prognosis: IPF-related interstitial pneumonia portends a worse prognosis and treatment
refractoriness compared to other interstitial pneumonias
diagnostic criteria: IPF is reserved for the clnical syndrome associated with usual
interstitialis pneumonia: heterogeneous appearance at law magnification, alternating areas of
normal lung, interstitial inflammation, and fibrosis.

3. Smokers lung
respiratory bronhiolitis associated with interstitial lung disease
desquamative interstitial pneumonia: intraalveolar collection of dusty brown
macrophages + patchy interstitial fibrosis
Photo: Desquamative interstitial pneumonia. Intraalveolar collection of dusty brown
macrophages + patchy interstitial fibrosis.

4. Diffuse alveolary hemorrhage syndromes
Goodpasture syndrome
idiopathic pulmonary hemosiderosis
vasculitis-associated hemorrhage
Wegener granulomatosis
microscopic polyangiitis
SLE

Photo: Goodpasture syndrome. Severe lung hemorrhage.
Photo: Goodpasture syndrome. Left: Punctuated hemorrhage in the kidney. Right: Crescentic
glomerulonephritis. Fibrin in a crescent. Linear IgG along the GBM.
Photo: Vasculitis-associated lung hemorrhage, pANCA+, pulmo-renal syndrome. Left:
intraalveolar hemorrhage: red blood cells in the lumen of alveoli. Right: hemosiderin laden
macrophages in the lumen of alveoli.

5. Bronchilitis obliterans (BOP):
Etiology, multifactorial: respiratory tract infection, inhaled toxin, drugs, collagen vascular
disease, idiopathic
Morphology: loose fibrous plug fills out the lumen of bronchioles.

Photo: Bronchilitis obliterans (BOP), loose fibrous plug fills out the lumen of bronchiole
Photo: bronchiolitis obliterans ang organizing pneumonia
loose fibrous plug fills out the lumen of bronchiole and alveoli.




6. Hypersensitivity pneumonitis

fungal and bacterial antigens:
farmers lung: moldy hay
humidifier or air-conditioner lung: thermophylic actinomycetes

animal products:
pigeon breeders lung: proteins from feathers or excreta

clinical coarse: acute, chronic


pathology:
bronchiolocentric interstitial pneumonitis with mononulear cell infiltrate, and
interstitial fibrosis
loosely formed noncaseating granulomas related to type IV hypersensitivity in two
thirds of cases
acute form + PNG infiltrate in
Photo: Hypersensitivity pneumonitis, farmers lung small granulomas in the lung.
Early cessation of exposure prevents the development of fibrosis!


7. Complication of Therapies

drugs pl Bleomycin
radiation
transplanted lung: rejection

8. Boeck sarcoidosis
multisystemic disease of unknown etiology
noncaseating epitheloid cell granulomas in any tissue


8. Boeck sarcoidosis

adults, younger than 40 years
women are involved more frequently than men
american blacks 1Ox more often than whites

clinically: variable, depends on the organ involvement


pathomechanism: cell mediated immunity plays a role against undefined antigen

Dg:
1. characteristic chest X-ray: bilateral hilar lymphadenopathy
2. lymph node or liver biopsy demonstrating noncaseating granulomas
Tbc and other granulomatous diseases should be excluded!


histology:
noncaseating epitheloid cell granulomas:
epitheloid cells, multinucleated giant cells, CD4+ lymphocytes and depending on the
age of lesion fibrosis
Schaumann bodies: laminated calcified proteinaceous concreations
Asteroid bodies: stellate inclusions within giant cells
Photo: Boeck sarcoidosis, lymph node noncaseating epitheloid cell granulomas.
Photo:Boeck sarcoidosis. Asteroid body: stellate inclusion within giant cell.


organ involvement:

lymph nodes: most commonly in the hilar region, bilateral hilar lymphadenopathy
lungs: diffuse scattered granulomas in the interstitium, heal with hyalinized small
scars
spleen and liver
skin, eye, parotis, bone marrow


clinical outcome:

7O% no or minimal residual manifestations
2O% permanent lung or ocular dysfunction
1O% die due to pulmonary fibrosis and cor pulmonale chr, cardiac failure



UPPER RESPIRATORY TRACT

Rhinitis

acute rhinitis ("common cold")
caused by adeno-, echo-, and rhinoviruses
produces erythematous and edematous nasal mucosa with profuse catarrhal discharge
may extend, producing a concomitant pharyngotonsillitis
bacterial superinfection can induce mucopurulent exudates

Allergic rhinitis ("hay fever")
affects 20% of individuals
it is an IgE-mediated immune reaction
mucosal edema and erythema, and eosinophil-rich infiltrates

Nasal polyps inflammatory pseudopolyps
occur after recurrent rhinitis attacks
edematous mucosa infiltrated by neutrophils, eosinophils, and plasma cells
when multiple or large, they obstruct the airway and impair sinus drainage,
necessitating removal
Photo: Nasal polyps inflammatory pseudopolyps. Edematous mucosa infiltrated
predominantly by eosinophyls

Chronic rhinitis
is a sequel to repeated attacks of acute rhinitis
may be microbial or allergic in origin
deviated nasal septum or nasal polyps predispose to infection
frequently there is superficial desquamation or ulceration of the mucosal epithelium
variable cellular infiltrate of neutrophyls, lymphocytes and plasma cells may be
present
suppurative infections sometimes extend into the sinuses

Sinusitis

commonly preceded by acute or chronic rhinitis
maxillary sinusitis can occur by extension of a periapical tooth infection through the
sinus floor
offending organisms are normal oral commensals (commonly mixed microbial flora)
diabetics can develop severe chronic sinusitis due to fungi (e.g.,mucormycosis)
In Kartagener syndrome, (congenitally defective cilia) is part of
the triad:
sinusitis
bronchiectasis
situs inversus

Photo: Chronic sinusitis. Heavy mononuclear cell infiltrate. Eosinophils are also present.

Nasopharynx Inflammation

Acut pharyngitis and tonsillitis
are frequent concomitants of viral upper respiratory infections
there is mucosal edema and erythema with reactive lymphoid hyperpalasia
bacterial superinfection exacerbates the process, particularly in immunocompromised
individuals or children without protective immunity

More severe forms of acute inflammation:
pseudomembranous nasopharingitis
follicular tonsillitis: enlarged reddened tonsils due to reactive lymphoid hyperplasia
and dotted pinpoints of exudate emanating from tonsillar crypts

Acut pharyngitis s tonsillitis, Streptococcal sore throats
caused -haemolyticus streptoccus
Major significance: late sequela
rheumatic fever
acute poststreptococcal glomerulonephritis

Laryngitis
can be caused by allergic, viral, bacterial, or chemical injury
most common causes are nonspecific infection or heavy tobacco smoke exposure
in children, Haemophilus infiuenzae laryngitis
Can be life threatening due to airway obstruction from rapid onset severe mucosal edema


Rare forms of laryngitis
tuberculotic
diphteric

Necrotizing Lesions of the Nose and Upper Airways
1. spreading fungal infections
2. Wegener granulomatosis
3. lethal midline granulomas; an angiocentric non-Hodgkin lymphoma called nasal T cell
lymphoma

Photo: Wegener granulomatosis. A. Oral mucosa: necrotising granulomatous inflammation
with vasculitis. B. Lung: necrotising granulomatous inflammation. C. cANCA+, indirect IF.
D. Kidney: crescentic glomerulonephritis

Tumors of the Nose, Sinuses, and Nasopharynx:
Nasopharyngeal angiofibroma
highly vascularized benign tumor
occurres in adolescent boys
serious bleeding can complicate surgical resection
Inverted papilloma
benign but locally aggressive neoplasm of squamous epithelium
Olfactory neuroblastomas
uncommon, highly malignant tumors
composed of neuroendocrine cells
Nasopharyngeal carcinomas: as discussed before