Chronic restrictive lung disease

**Chronic inflamation of lung parenchyma

and or interstitium leading to progressive
fibrosis of the lung.
Characteristic features
1.Reduced Total lung capacity
2.Reduced FVC
3.Reduced FEV1
4.Normal FEV1-to-FVC ratio

**Many are due to unknown cause and pathogenesis.

Known causes are
1.Occupational-Organic dustAsbestos,Silica,Coal
-InorganicHypersensitivity pneumonitis
2.Drugs-Chemo drugsBusulphan,Bleomycin,Methotryxate
-Ionising radiation,higher % of O2 treatment.
3.Immunological-Sarcoidosis,Wegeners granulomatosis
Goodpasture syn, Allograft rejection
Collagen vascular disease
SLE, Rheumatoid.A, Scleroderma
Dermatomyositis,polymyositis
4.MisselaneousIdiopathic,Post ARDS.

**The common end result of most of these causes

would be diffuse interstitial pulmonary fibrosis
with or without honeycombing(so biopsy in late
disease will not help to find the cause).
**Biosy in early disease may show granulomas or
foreign material which may help find the cause.
occupational and social history of these patients
are very important to find the cause.

Idiopathic Pulmonary fibrosis

(Interstitial pneumonia)
*It is also called as cryptogenic fibrosing alveolitis.
*Aetiology not known.
*Immune mediated reaction to unknown antigen
may be the one trigering this inflamation

*M > F, common in > 60 years of age.

*As there are lot of disease conditions which can
cause interstitial fibrosis,We need to exclude
other known causes before making a
a diagnosis of Cryptogenic fibrosis.

Unknown antigen

B lymphocyte
Immunoglobulin
immune complex

T lymphocyte

cytokines

Antigen

Activated macrophage
Fibrogenic &chemotactic ck
Recruitment of N
Fibroblast
Oxidants proteases
Fibrogenic &Chemotactic
Cytokine

Injury to type 1 pneumocyte

Hypertrophy & hyperplasia of Type 2 cells

Pathogenesis

Alveolar epithelial cell injury due to unknown antigen/

Ag-Ab complex
Inflamatory oedema & accumulation of cells-N,L,M
Mediators released by Macrophage recruit N.
The mediators of N & M Injure alveolar epithelium
and degrade conective tissue
Persistant inflamation and release of mediators leads to
proliferation of fibroblast and progressive interstitial fibrosis.
Destruction of type 1 pneumocyte is accompanied by
proliferation of type 2 cells
These type 2 cell produce chemotactic factor that attract
macrophages and T lymphocyte which also contribute for
fibrosis by producing fibrogenic cytokines

Macroscopy
Small volume of lung
Cut surface Honeycomb appearance
Microscopy-:
Alternating area of normal, interstitial
inflamation & fibrosis will be seen.
Inflamation in patchy in nature consist of
alveolar septal infiltrate of Lymphocytes
Damaged Type 1 pneumocyte with hyperplasia
of Type 2 pneumocytes

 Fibrotic area contain acellular dense collagen.

In advanced stages air spaces are lined by Type 2
pneumocytes separated by inflamatory fibrous
tissue Honeycomb apppearance(not specific to
idiopathic, can occur in any form of diffuse fibrosis)
Clinical features
Gradual onset of dry cough and SOB
In late stage features of right heart failure pedal oedema
O/E:- Clubbing & bilateral basal fixed dry crepts
may be cyanosed with pedal oedema, JVP
Diagnosis:- Spirometry, Cxray, HRCT

Sarcoidosis
Granulomatous disease involving multiple organs
Characterised by noncaseating granuloma.
Unknown aetiology
But thought to be due to disordered cellmediated
immune reaction to unknown antigen in genetically
predisposed individuals.
*Commonly present with bilateral hilar LN enlargement and
or lung infiltrate.
* cimmon in < 40 years & nonsmokers.

Theoretical Aetiology and pathogenesis

Disordered immune regulation in genetically
predisposed individuals exposed to certain environmental
Antigens.
Evidence for this
Immune
Genetical
Environmental
1. alveolar CD4 T cells
* Familial &
*Association
2. TH 1 cytokines-IL1& 8
clustering
with virus
TNF & interferone
*Association with Mycobacteria
3. CD4 : CD8 ratio
HLA-B8, A1
Borrelia
4. Anergy to skin test
Pollen
Mx test
5.Hypogamaglobulinaemia

Organs that could be affected

1. Lung
2. Lymph nodes, skin
3. Eye & lacrimal gland
4. Parotid glands
5. Spleen, Liver
6. Bone, Bone marrow
All these organs can have non caseating
granuloma

Other diseases in which non caseating

granuloma could be seen are
1. Fungal infection
2. Berylliosis
3. Lymphomas
4. Rarely TB
These granuloma can secret
1. Active vitamin D Ca absorption
2. Angiotensin converting enzyme
3. Gamma globulins

Histology of Granuloma
1. At the centre of granuloma epithelioid
histeocytes (differentiate mononuclear monocytes)
2. In between those cells multi nucleate
Giant cells (fused macrophages)
3. This will be surrounded by CD4-B
lymphocytes
4. Out side this active fibroblast surrounding
the granuloma will be seen
5. Fibroblast produce hyaline also could be
seen
6. In late stage this hyaline material will
replace all the granuloma & becomes

7. Rarely central necrosis seen but no

caseation
8. Within the Giant cells can see
a. Schaumann bodies Ca++ & protein debris
b. Asteroid bodies
Organs involved & problems
1. Lung Affected I 90% of the patients
granuloma seen in interstitium around bronchiloe,
pulmonary venules and pleura
In chronic cases leads to intestitial fibrosis &
honey comb lung

They present with sob & or dry cough

Usually asymptomatic
2. Lymphnode
commonly cause hilar & paratacheal
enlargement
Can cause peripheral lymphnode
enlargement
Lymphnodes are painless, firm, non matted,
do not ulcerate
They may be asymptomatic or present with
fever, fatigue, weight loss or night sweats

3. Skin
a. Erythema nodosum raised red tender
nodules over anterior aspect of legs.
No granuloma seen in this lesion.
b. Descrete painless subcutaneous nodules
Granuloma is seen in this lesion
c. Lupus pernio Indurated plaques with
violaceous discolourasion seen over nose
cheeks & lips
Granuloma is seen in this lesion

4.Eye
a. Iritis corneal of opasity loss of vision
b. Iridocyclitis glaucoma
c. Posterior uveitis, choroiditis, retinitis
d. Optic neuritis
e. Lacrimal gland reduced lacrimation leads
to dry eye called as sicca symdrome
They may complain irritation of eye, redness
or loss of vision

5. Parotid glands
Unilateral/bilateral painfull enlargement of
parotid gland
In late stages reduction salivation leads to
dry mouth called as xerostomia
6. Spleen & liver involvement
May cause hepatosplenomegaly
7. Bone marrow involvement may lead to
anaemia or pancytopenia
I

8. CNS involvement may lead to various

neurological deficit including mononeuritis
9. Renal involvement leads to renal impairment
Some patients would be diagnosed on routine
investigation for medical
Some patients present with Uvitis & parotid
involvement called as uveoparotid fever or
mikulicz syndrome
Diagnosed with biopsy, demonstrating non
caseating granuloma with exclusion of other
causes for granuloma