Intrestitial lung disease 16 5-2016

Interstitial Lung Disease &Pulmonary Infection

Dr. Vinita Singh

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.

Cond,

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

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.

Cond,

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

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)

Secondary Causes1.Infectious• Tuberculosis• Bacterial• Fungal• Parasitic• Viral2. Noninfectious• Hypersensitivity pneumonitis• Pneumoconiosis• Drug induced• Radiation induced• Malignancies

Association with diseases of unknown aetiology

• Sarcoidosis• Connective tissue disorders• Systemic sclerosis• Rheumatoid arthritis• Dermatomyositis,Polymyositis• SLE• Chronic eosinophilic pneumonia

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.

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

fibrosisIIP 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.

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.

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 lungresponses to inhaled agents

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

Thannickal VJ, et al. Annu Rev Med. 2004;55:395-417.

AGEGENETIC FACTORS

ENVIRONMENTAL FACTORSNATURE OF INJURY

– Etiologic agent– Recurrent vs single

– Endothelial vs epithelial

Histopathologic Pattern

DIP RB-ILD LIP COP NSIP AIP UIPInflammation Fibrosis

LUNG INJURY

PATTERNS ON CHEST X-RAY

LINEAR

reticular

NODULAR

RETICULONODULAR

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

IPF

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 ?

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 ?

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.

Cont’

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

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.

• 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.

• ExudateThe 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.

Types• Viral• Bacterial• Mycoplasmal• Fungal

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

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

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.

• 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.

• 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.

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. Lobar pneumonia

•1.3. Viral (Atypical) pneumonia

Bronchopneumonia

Bronchopneumonia

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).

• 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.

• 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".

• 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.

• 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.

Lobar Pneumonia

Lobar Pneumonia – Gray hepatization