1. The document discusses several cases of interstitial lung disease and pulmonary infection. Case 1 describes a man with nodularity and calcification found on chest x-ray, with biopsy revealing birefringent particles. 2. Case 2 involves a retired shipyard worker with shortness of breath and pleural plaques on CT, with dumbbell-shaped structures staining blue. 3. The document then reviews the etiology, pathogenesis, clinical features, patterns on imaging, and pathology of various forms of interstitial lung disease and pulmonary infections like bacterial pneumonia.

1. Interstitial Lung Disease &
Pulmonary Infection
Dr. Vinita Singh

2. CASE-1
A routine chest X- ray performed on an asymptomatic
adult man who works at sandblasting reveals a fine
nodularity in the upper zone of the lung and “eggshell”
calcification of the hilar lymph nodes.
The Pt. S.calcium level is 9.8m/dl total protein is7.2g/dl.
He denies any H/O drug use or ciggarette smoking.

3. Cond,
A biopsy from lung reveal birefringent
particles within macrophages and fibrosis of
lung.
what is the material ?

4. CASE -2
A 65yr old man who just retired after having
worked for many years as a shipyard worker
presents with increasing shortness of breath.
Pertinent medical history is that he has been
a long time smoker.
A CT Scan of his chest reveals thick , pleural
Plaques on the surface of his lungs.

5. Cond,
The Dumbbell – Shaped structures were found
to stain blue with a prussian blue stain .
What are these structures ?

6. IMPORTANT CAUSES OF ILD
1. Primary or idiopathic
• Idiopathic Pulmonary Fibrosis
• Nonspecific interstitial pneumonia (NSIP)
• Organising pneumonia (OP)
• Respiratory bronchiolitis (RB)
• Diffuse alveolar damage (DAD)
• Desquamative interstitial pneumonia (DIP)
• Lymphocytic interstitial pneumonia (LIP)

7. Secondary Causes
1.Infectious
• Tuberculosis
• Bacterial
• Fungal
• Parasitic
• Viral
2. Noninfectious
• Hypersensitivity pneumonitis
• Pneumoconiosis
• Drug induced
• Radiation induced
• Malignancies

8. Association with diseases of unknown
aetiology
• Sarcoidosis
• Connective tissue disorders
• Systemic sclerosis
• Rheumatoid arthritis
• Dermatomyositis,Polymyositis
• SLE
• Chronic eosinophilic pneumonia

9. ILD is a heterogeneous syndrome with the following
common clinical features:
1. Exertional dyspnea
2. Bilateral diffuse infiltrates on chest radiographs
3. Physiological abnormalities with a restrictive lung defect,
decreased diffusing capacity (DLco) and abnormal alveolar-
arterial oxygen gradient (PAO2 – PaO2) at rest or with exertion.
4. Absence of pulmonary infection and neoplasm.
5. Histopathology with varing degrees of fibrosis and
inflammation with or without evidence of granulomatous or
secondary vascular changes in the pulmonary parenchyma.

10. Diffuse Parenchymal Lung Disease (DPLD)
DPLD of known cause, eg,
drugs or association, eg,
collagen vascular disease
Idiopathic
interstitial
pneumonias
Granulomatous
DPLD, eg,
sarcoidosis
Other forms of
DPLD, eg, LAM,
HX, etc
Idiopathic
pulmonary
fibrosis
IIP other than idiopathic
pulmonary fibrosis
Desquamative interstitial
pneumonia
Acute interstitial pneumonia
Nonspecific interstitial
pneumonia (provisional)
Respiratory bronchiolitis
interstitial lung disease
Cryptogenic organizing
pneumonia
Lymphocytic interstitial
pneumonia
ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

11. PATHOLOGY
• Pulmonary interstitium is the anatomical space
between the alveolar and the capillary basement
membranes.
• Contains mesenchymal and connective tissue
cells and extra cellular matrix composed of
collagen, elastin and proteoglycans.
• Involvement of interstitium+ adjoining alveolar
epithelial+ Capillary endothelial cells.
• Disease encroaches alveolar spaces involving
acini, terminal bronchioles and overlying pleura.

12. Inhaled environmental agents
(fumes, dust, smoke)
Alveolar epithelial cell injury
Wound healing (inflammation,
coagulation, epithelial/endothelial
repair)
Pulmonary
fibrosis
Normal
Chronic airflow
obstruction
Genetic
predisposition
Delivery
&
persistence
Biochemical
Immunologic
Fibrotic
Four proposed mechanisms and potential variations in lung
responses to inhaled agents

13. Recent Hypothesis:
• Inflammatory hypothesis
• Epithelial Cell Apoptosis
• Angiogenesis
• Abnormal Matrix Turnover
• Th1 versus Th2 Cytokines
• Growth Factor Production
• Altered Fibroblast Phenotypes
• Myofibroblast Recruitment and Maintenance

14. Thannickal VJ, et al. Annu Rev Med. 2004;55:395-417.
AGE
GENETIC FACTORS
ENVIRONMENTAL FACTORS
NATURE OF INJURY
– Etiologic agent
– Recurrent vs single
– Endothelial vs epithelial
Histopathologic Pattern
DIP RB-ILD LIP COP NSIP AIP UIP
Inflammation
Fibrosis
LUNG INJURY

15. PATTERNS ON CHEST X-RAY
LINEAR

16. reticular

17. NODULAR

18. RETICULONODULAR

19. Normal Lung- cut surface and pleura smooth and homogenous
IPF- cut surface demonstrates patchy involvement of lung with fibrous scarring
around dilated airspaces forming a honey comb pattern
IPF

20. CASE-3
A 24yr old African American woman presents
with nonspecific symptoms including fever
malaise.
A chest X –ray reveals enlarged hilar lymph
nodes ( potato nodes) .
serum calcium level is found to be elevated
What is the probable diagnosis ?

21. CASE -4
A 61yr old man presents with increasing
shortness of breath .
A chest X- ray reveals diff. Pulmonary infiltrate.
transbronchial biopsy reveals fibrosis of the
walls of the alveoli, many of which contain
sheets of “ desquamated’’ cells.
What is the probable diagnosis ?

22. CASE -5
A 37yr old woman presents with acute onset
of a productive cough, fever, chills and pleuritic
chest pain.
A chest X –ray reveals consolidation of the
entire lower lobe of her right lung .
Histologic examination of lung tissue reveals
multiple suppurative , neutrophil – rich exudates
filing bronchi , bronchioles and alveolar spaces.

23. Cont’
1. What is the probable diagnosis?
2. What is the etio – pathogenesis ?

24. Etiology
• 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 competence.

25. • An increased risk of bacterial
infection is associated with impairment
of the defense mechanism, as in any of
these clinical situations:
– Loss of consciousness
– Immunodeficiency state
– Pulmonary edema
– Neutropenia
– Chronic airway obstruction
– Viral infection.

26. • Exudate
The exudate in bacterial pneumonia is
typically composed of varying proportions of:
– 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.

27. Types
• Viral
• Bacterial
• Mycoplasmal
• Fungal

28. The Pneumonia Syndromes
• Community-acquired
acute pneumonia
– Streptococcus pneumonia
– Haemophilus influenza
– Moraxella catarrhalis
– Staphylococcus aureus
– Legionella pneumophilia
– Klebsiella
– Pseudomonas
• Community-acquired
atypical pneumonia
– Mycoplasma
– Chlamydia
– Legionella
– Viruses (RSV,
parainfluenza & influenza,
adenovirus)
• Nosocomial pneumonia
– Gram negative rods
– Staphlyococcus aureus
• Aspiration pneumonia
– Anaerobic oral flora
– Amniotic fluid
– Gastric content
– Chemicals
• Chronic pneumonia
– Nocardia
– Actinomyces
– Granulomatous
• Necrotizing pneumonia
– Anaerobic
– Staphlyococcus aureus
– Klebsiella
– Streptococcus pyogens

29. 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.
Routes of Infection

30. Etiopathogenesis
• 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.

31. • 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.

32. • 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.

33. • 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.

34. • Aspiration pneumonia is observed in
individuals with altered sensorium (eg,
seizures, alcohol intoxication, drug
intoxication) or CNS impairment (eg,
stroke).
– The stomach or oropharyngeal contents are
aspirated.

35. 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

36. 1. Pneumonia
•1.1. Bronchopneumonia
•1.2. Lobar pneumonia
•1.3. Viral (Atypical)
pneumonia

37. Bronchopneumonia

38. Bronchopneumonia

39. 1.2. Lobar Pneumonia
• 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).

40. • 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.

41. • 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".

42. • 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.

43. • 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.

44. Lobar Pneumonia

45. Lobar Pneumonia – Gray hepatization