RESPIRATORY PATHOLOGY

ATLANTIC UNIVERSITY SCHOOL OF MEDICINE

 Pulmonary Infections
More frequent than infections of any other
organ
Majority are upper respiratory tract
infections caused by viruses (common
cold, pharyngitis)
Lower respiratory infections can be
bacterial, viral, mycoplasmal and fungal
lung infections (pneumonias)
Pneumonias account for much morbidity
& are responsible for 1/6 of all US deaths
 Pneumonia
Broadly defined as any infection of
the lung parenchyma
Another term is pneumonitis
 Case Records of the Massachusetts General Hospital
Cas30-Year-Old Woman with Shock after Treatment
of a Furuncle
Moellering, Jr., Gerald F. Abbott, and Mary Jane Ferraro,

A 30-year-old woman was transferred to

this hospital because of hypotension and
respiratory failure.
One month earlier, cultures of an abscess
on her leg grew MRSA; antibiotics were
prescribed and the abscess resolved.
On the day of admission, the patient was
found unresponsive at home.
N Engl J Med, Volume 364(3):266-275, January 20, 2011
 Final Diagnosis

Sepsis due to community-acquired

methicillin-resistant Staphylococcus
aureus, strain USA300-0047, PVL-
positive.
Lung- defense mechanisms

Joshi lung 1 Bhusnurmath

Lung- Clearing mechanisms
interfered with
Injury to Mucociliary apparatus(cigarette smoke,
inhaling hot or corrosive gases, viral diseases,
genetic disturbances)
Loss of Cough reflex (comma, anesthesia,
neuromuscular disorders, drugs, chest pain)
Interference with phagocytic or bacterial action
of alveolar macrophages (alcohol, tobacco
smoke, anoxia, oxygen intoxication)
Pulmonary congestion and edema
Accumulation of secretions (cystic fibrosis,
bronchial obstruction)
Lung- defense mechanisms
Immune opsonins (alveolar
macrophages)
C3b, IgA, IgG
T lymphocytes normally in airspaces
Neutrophils (not normal), easily
recruited
 Secondary pneumonia
Underlying abnormality predisposes
Postoperative (ventilation reduced)
Smoking (mucociliary reflex)
Aspiration (due to loss of cough and
swallowing reflex)
Preexisting lung disease - viral
infection, emphysema, bronchiectasis
Immunosuppression
Secondary pneumonia contd.
Bronchial obstruction- tumor, foreign
bodies
Coma - cough reflex lost
Alcoholics, diabetes
 Clinical - pneumonia
Abrupt high fever, cough, rusty
purulent sputum
Chest pain, pleural rub (if there is
pleuritis)
air entry, consolidation, X- ray
Microbe - sputum, blood
 Pneumonia-classifications
Primary/Secondary, Acute/Chronic,
Necrotizing,
Mode of infection-
community acquired, hospital
acquired/nosocomial, aspiration
Site of action- alveolar space (typical),
alveolar wall (atypical)
Microorganism- Bacterial, Viral,
Chlamydia, Fungi etc
 Pneumonia Syndromes (7)
Community-Acquired
Acute Pneumonias
Atypical Pneumonias
Hospital acquired/Health care acquired*
Aspiration Pneumonias
Chronic pneumonias
Necrotizing Pneumonias and Lung Abscess
Pneumonia in the immunocompromised hosts

* Nursing home, rehabilitation centers

The Pneumonia Syndromes
Community acquired
Acute Pneumonia
Healthy person/Virulent organism
Strep. pneumonia, Hemophilus,
Moraxella, Staph, L. pneumophilia,
Klebsiella and Psuedomonas
Atypical pneumonia
Mycoplasma, Chlamydia, Coxiella
Burnetti, and viruses (influenza)
The Pneumonia Syndromes
Hospital/Heath care facility
Acquired Pneumonias
Nosocomial
Gram negative rods belonging to
Enterobacteriaceac-Klebsiella,
E.coli, Pseudomonas
Staph Aureus (MRSA)
Immunosuppression, antibiotics,
catheters, ventilators
The Pneumonia Syndromes
Aspiration pneumonias
Acid
Occur in those who aspirate gastric contents
(either while unconscious or by vomiting)
Frequent cause of death those who survive,
a common complication is lung abscess
formation
Mixed nature of organisms
Anaerobic oral flora and Aerobic
organisms
The Pneumonia Syndromes
Aspiration Pneumonia

-Anerobic oral flora

-Bacteroides, Fusobacterium,
Peptostreptococcus
-Aerobic
-Strep, Staph, H. Influenzae,
Psuedomonas
The Pneumonia Syndromes
Chronic Pneumonia
Nocardia
Actinomyces
Granulomatous
MTB, Atypical Mycobacterium
Fungal
Histoplasma,Coccidioides,
Blastomyces
The Pneumonia Syndromes
Necrotizing Pneumonia and Lung
Abscess

-Anaerobic(extremely common)
-Staph Aureus, , Klebsiella,
Streptococcus pyogenes
The Pneumonia Syndromes

Pneumonia in the immuno-

compromized host
Cytomegalovirus
Pneumocystis
Mycobacterium avium intracellulare (MAI)
Invasive aspergillosis, invasive candiadiasis
Usual bacterial pneumonias
 Case 1
48 yr male presents with a mass lesion
in his left lower lobe
Clinical diagnosis malignancy
Wedge resection is performed
 Diagnosis
Frozen section diagnosis
Necrotic tissue; no tumor seen
Final diagnosis
Tuberculosis of Lung
Special stains for Acid fast bacilli were
positive
 Case 2
19 year old with a bronchoscopic
biopsy of a lung lesion
 Diagnosis
Granulomatous inflammation
Accompanying bronchial washings
showed 4 + acid fast bacilli
 Case 3
47 yr female with bilateral interstitial
lung infiltrates
 Diagnosis
Pneumocystis Pneumonia
 Case 4
55yr old with bilateral lung disease,
unknown etiology
 Diagnosis
Acute Bronchopneumonia
 Complications of
Pneumonia: Empyema

Decortication performed for

complications of Pneumonia
 Pneumonia
Site of action-
alveolar space
bacterial
alveolar wall
atypical
viral
Air space pneumonia

Joshi lung 1 Bhusnurmath

 Lobar Pneumonia
Large confluent areas of
consolidation
Almost whole lobe
Bronchi not involved
Spread through pores of Kohn
Usually virulent organism- Strep.
pneumonia
 Bronchopneumonia:
bronchi + surrounding alveoli
Patchy
Usually less virulent organisms
bronchi, bronchioles also damaged
intervening areas normal
less chances of pleuritis
 Pneumonia: stages
Both lobar and broncho pneumonia
go through 4 stages if untreated
Antibiotics halt the process
 Acute Congestion
heavy red boggy
lungs

bacteria multiply in
alveoli, dilated
alveolar capillaries,
early fluid exudation

early PMNs + early

red cells
 Red Hepatization
consistency liver like

lining alveolar cells lost

PMNs, fibrin, red cells

Pleuritis

infection controlled
 Gray hepatization
dry, gray, firm

exudation and
hyperemia stop

red cells
depleted
 Resolution

Removal of exudate
complete resolution can occur
because structure of alveoli not
damaged in lobar pneumonia
Bronchopneumonia has structural
damage
 Complications of pneumonia
Pleural effusion
Lung abscess: anaerobic bacteria,
Staphylococcus aureus, Klebsiella
pneumoniae, Streptococcus
pyogenes
Empyema
Meningitis, bacteremia, endocarditis,
arthritis
 Lung Abscess
Copious, foul sputum, hemoptysis,
fever, malaise
Complications bronchopleural
fistula, empyema, septicemia,
amyloidosis
Treat with antibiotics
 Psuedomonas aeroginosa
Cystic fibrosis
Nosocomial, neutropenic patients,
burns
Vasculitis and vascular spread
Psuedomonas septicemia is a very
fulminant disease
Staph. aureus pneumonia:
After viral respiratory illness -
secondary
Nosocomial (MRSA Penicillin
resistance)
Abscess formation, empyema
I/V drug abusers- endocarditis
 Klebsiella Pneumonia
Most frequent gram negative
pneumonia
Debilitated and malnourished
Chronic alcoholics
Thick gelatinous sputum ( viscid
capsular material)
Extensive destruction
 Moraxella catarrhalis
Elderly individuals
Second most common cause of
pneumonia in COPD
Otitis media in children
 Pneumococcal pneumonia
Settings- usually nil, viral infection,
CHF, COPD, immune
deficiency, splenectomy (auto)
Sputum - gram positive diplococci- look
for intracellular in pmn
Blood culture - more specific
Vaccines
 H. Influenzae pneumonia
After viral respiratory illness - secondary
Common cause of community acquired
pneumonia in adults
With routine use of the vaccine, the
incidence of disease caused by the b
serotype has decreased significantly
Can cause endocarditis
Most common cause of acute
exacerbation of COPD
 Legionella pneumonia
Sporadic, epidemic
Artificial water pools- tubing, cooling
towers
In chronically ill patients, post
transplant
High fatality
Culture- best for diagnosis, others-
sputum, urine
Vascular and Hemodynamic
Pathology
Topics Covered In This
Lecture
1.Pulmonary Edema
2.Acute respiratory distress
syndrome (ARDS)
3.SARS (Severe acute
respiratory syndrome)
4.Pulmonary Embolism
5.Pulmonary Hypertension
 Case History
72 yr old extremely pleasant
Caucasian male with a past medical
history of CABG and multiple stents,
unstable angina and myelodysplastic
syndrome, presented with left arm
pain
He was admitted, but died within 24
hours
A post mortem was performed.
 Post mortem findings
Right lung weighed 1,100 g and the
left lung weighed 750 g
Severe coronary atherosclerosis was
noted
There was evidence of acute
myocardial infarction and massive
pulmonary edema
 Causes of Pulmonary
Edema
Hemodynamic disturbances
Increased hydrostatic pressure
Left sided congestive heart failure
Heavy wet lungs (basal regions of lower lobes)
Alveolar capillaries engorged
Intra-alveolar granular pink precipitate
Heart failure cells; brown discoloration
Impairs pulmonary function and predisposes
to infection
 Pulmonary Edema- Causes
Hemodynamic
Increased hydrostatic pressure
Left ventricular failure (common)
Excess IV fluids
Decreased oncotic pressure
Severe hypoproteinemia, Liver disease,
Nephrotic syndrome
Other
Lymphatic obstruction (carcinoma, rare)
 Pulmonary edema--Causes

Microvascular Injury
Damage to vascular endothelium
Leekage of fluid and proteins into
interstitium and lumen
Diffuse edema is a contributor to
acute respiratory distress syndrome
 Microvascular injury
Infections: Pneumonia, septicemia
Inhaled gases: Oxygen, smoke
Liquid aspiration: Gastric contents
Drugs and chemicals:Chemotherapy
agents, heroin, cocaine, paraquat
poisoning
Shock, trauma
Radiation
Transfusion related
 Adult(Acute) Respiratory
Distress Syndrome (ARDS)
Syn. Shock Lung Syndrome, Diffuse
alveolar damage (DAD), Acute lung
injury (ALI)
(cf. RDS in neonates due to
deficiency of surfactant)
Clinical syndrome caused by diffuse
alveolar damage
 Mechanism of ARDS
Imbalance between pro-inflammatory
and anti inflammatory cytokines
Toll like receptors activate NF-kB, a
transcription factor controlling
expression of pro-inflammatory
genes
IL-10 is anti-inflammatory cytokine
Modification of the transcription
cascade may be a logical future
target for ALI
ARDS
ARDS
Endothelium
necrosis
Type I alveolar
cells necrosis
Fibrin
Edema
Waxy Hyaline
membranes
 Shock lung
Endothelial damage, damage to type 1
pneumocytes
Exudate, impaired gas exchange
Hyaline membrane (necrotic debris from
epithelial cells plus edema fluid coagulate)
Type II pneumonocyte necrosis- loss
of surfactant- microatelectasis
 What Causes ARDS?
Infections*
Sepsis*
Head injuries*
Gastric aspiration*
Pancreatitis
Burns
Trauma
Fractures with fat embolism
 Clinical features

Serious disorder
Respiratory difficulty- acute
Gasping for breath
Severe hypoxemia, cyanosis, unresponsive to
oxygen
Bilateral infiltrates on chest X-ray
Absence of clinical features of LVF
High mortality: 40% in 190,000 ARDS cases/yr
Patchy distribution
Healing may result in diffuse interstitial fibrosis
 Phases of ARDS
Exudation- 0-7 days
Proliferation - 1-3 weeks
macrophages phagocytose dead
cells and hyaline membrane, type
II pneumonocytes proliferate
mature in to type I cells
Fibrosis- TGF-, PDGF
 SARS
(Severe acute respiratory syndrome)
First appeared in China in Nov 2002; last case 2004
Cause -- Corona virus; 8000 cases; 774 deaths
2-10 day incubation period;begins with dry cough,
malaise, myalgia, fever, chills
1/3rd fight infection, but 2/3rd progress to severe
respiratory disease, shortness of breath, tachypnea,
and pleurisy
10% of patients die from illness
First transmitted through wild masked palm civets
Patho-physiology unknown; how virus moved from
animals to humans unknown
 Pulmonary embolism
Pulmonary Infarction
Causes more than 50,000 US deaths/year
Large pulmonary embolus is a cause
sudden instantaneous death
Blood clots that occlude large pulmonary
vessels are embolic
Usual source of pulmonary emboli are the
deep veins of the leg
 Pulmonary embolism
95% from deep leg veins
Sick, bedridden patients with
pulmonary, cardiovascular
disease
BIG -> bifurcation of PA, sudden
death from acute right heart
failure - no time to develop any
changes in lungs
 Pulmonary embolism
MEDIUM -> hemorrhage, infarction
only if circulatory status already
compromized
SMALL -> usually no infarct because
of dual supply, resolve ( lysis),
if recurrent- pulmonary hypertension
 Infarction
Clinically resembles myocardial
infarction - chest pain, dyspnea,
shock
Gross: Wedge shaped, hemorrhagic
infarct, may be multiple
Micro: coagulation necrosis
Pulmonary Hypertension
 Case Vignette
47 yr old male, non-smoker presents
with worsening and progressive
dyspnea
On exam., bi-basilar crackles,
rhonchi and wheezes were noted
Past history is significant for
Osteogenesis Imperfecta, Spinal mid
thoracic kyphoplasty, hip and knee
surgery
 Case Vignette
Patient also has renal failure,
cardiomegaly, pleural effusion,
coronary atherosclerosis and
pulmonary edema
CT scan shows bilateral interstitial
infiltrates
Bronchosopic biopsies to rule out
interstitial disease/ infection
 What does the patient have?
Pulmonary hypertension
Pulmonary edema
Heart failure Cells (cor pulmonale)
No interstitial disease
No atypical pneumonia
 Pulmonary hypertension
When pulmonary pressure reaches 1/4th
of systemic levels
Primary- BMPR2 locus mutations
Rare, young women,recurrent
dyspnea ,syncope
Reynauds phenomenon (vasopasm
of peripheral vessels)
? Neurohormonal hyperactivity
? Vasotropic virus- HSV 8
 Pulmonary hypertension
Secondary
COPD - Chronic bronchitis,
emphysema, diffuse fibrosis
Congenital shunts- VSD
Recurrent pulmonary
thromboembolism in small sized
vessels
 Pulmonary hypertension

Mild
Elastic
Normal duplication
pulmonary Medial
artery hypertrophy,
Intimal fibrosis
Severe -
Plexiform
lesions
Pulmonary hypertension
Plexiform lesions
 Morphology of pulmonary
hypertension
Changes in medium sized arteries
Medical thickening
Intimal hyperplasia / fibrosis
Reduplication of elastica,
 Morphology of pulmonary
hypertension
Plexiform changes in severe
varieties only (primary)
Necrosis of wall (fibrinoid)
Thrombosis
Rupture, bleed
Dilation lesions, angiomatoid
lesions
Hemosiderin
 Primary pulmonary hypertension-
clinical
Symptoms appear late
Fatigue, dyspnoea
Syncope on exercise
Chest pain
Respiratory insufficiency, cyanosis
Cor pulmonale
Restrictive lung disease
 Case history
69 yr female with 3 month history of
dyspnea (shortness of breath)
Lung CT shows bilateral interstitial
infiltrates
A bronchoscopic biopsy is performed
 Diagnosis
Restrictive lung disease
Usual Interstial Pneumonitis with end
stage lung disease
Honey comb lung
 Restrictive lung disease
Extrinsic causes
Intrinsic causes
 Extrinsic
Chest wall injury,deformity
( kyphoscoliosis)
Severe obesity
Neuromuscular (Guillain Barre
Syndrome)
 Intrinsic
Acute - with known cause
ARDS following shock, pancreatitis
Acute - without known cause AIP
Chronic- without known cause
Idiopathic Interstitial Pneumonias
UIP, DIP/RBILD, NSIP, LIP, COP
Chronic with known cause
Pneumoconiosis
Immunologic
Sarcoidosis
Hypersensitivity pneumonitis
 International Consensus Classification
Idiopathic Interstitial Pneumonitis

Formulated in 2002
7 categories
No BOOP
Instead COP
 International Consensus
Classification
Histologic Patterns
2002Clinical-radiologic diagnoses

Usual Interstitial Pneumonitis (UIP) Idiopathic Pulmonary fibrosis (IPF)

Desquamative Interstitial Pneumonia (DIP) Desquamative Interstitial Pneumonia (DIP)

Respiratory bronchiolitis Respiratory bronchiolitis interstitial lung

disease (RBILD)
Diffuse alveolar damage (DAD) Acute interstitial pneumonia (AIP)

Non-specific interstitial pneumonia (NSIP) Non-specific interstitial pneumonia (NSIP)

Organizing pneumonia Cryptogenic organizing pneumonia (COP)

Lymphoid interstitial pneumonia (LIP) Lymphoid interstitial pneumonia (LIP)

Restrictive lung disease
 Introduction
Lung stiff, hard, difficult to expand
Diffusion across blood air barrier is
difficult
Referred to as interstitial lung
disease
 Restrictive lung disease
Acute - Adult respiratory distress
syndrome (vascular), AIP
Chronic - many entities
FEV1 , FVC , FEV1: FVC ratio
normal
Obstructive vs Restrictive

<70%

FEV1 : FVC
>70%
 Restrictive lung disease
Idiopathic-IPF, UIP, NSIP etc
Occupational- inorganic-
pneumoconiosis, organic-
hypersensitivity pneumonitis
Drug- chemotherapy, radiation,
oxygen therapy
Immunological- autoimmune
diseases, sarcoidosis
 Idiopathic pulmonary fibrosis
Clinical-Radiologic diagnosis
Usual interstitial Pneumonitis histologic
pattern; chronic disease
Acute form is Hamman Rich Syndrome
(AIP, acute interstitial Pneumonitis/DAD)
(Honey comb Lung; end stage disease)
Cause not known
Diffuse fibrosis in alveolar septa
M>F
40-70 years age
 Idiopathic pulmonary
fibrosis/UIP

Probably starts as alveolitis

damage to type I epithelial cells
Proliferation of type II cells
Fibrogenic cytokines
Fibrosis
 Idiopathic pulmonary
fibrosis/UIP
Type II cells-
Replace type I cells
Secrete chemotactic factors for
macrophages, T cells
Contribute to fibrosis by secreting
PDGF and TGF-
 Pathology - IPF/UIP
Early view was chronic inflammation led
to fibrosis
Now thinking favors repeated attacks of
alveolitis with wound healing
Wnt B catenin pathway is involved.
TGF-B is expressed
Increased septal and pleural fibrosis
Honey comb lung
 Clinical IPF/UIP
Progressive dyspnea, hypoxia,
cyanosis, pulmonary
hypertension
Bilateral basal lesions
CT- early detection of IPF, exclude
other causes of pulmonary fibrosis
subpleural wedge biopsy- image
guided
 Clinical IPF/UIP
Cor pulmonale- JVP, edema
Progression- variable
Death in 2-4 years
Similar end result in many ->
rheumatoid arthritis, systemic
sclerosis, SLE etc.
Honey comb- systemic sclerosis
Systemic sclerosis
Types of interstitial
pneumonia
 Case history

40 yr old
male smoker,
presents
with dyspnea
CT shows
bilateral
interstitial
infiltrates
 Case history
48 yr old female with bilateral lung
infiltrates simulating pneumonia
 Diagnosis

RBILD
Respiratory bronchiolitis interstitial lung
disease
 Case history
52 years female with bilateral interstitial
infiltrates
Patient is HIV positive, and Hepatitis C
positive
Patient has a past history of
Pneumocystis Pneumonia
 Diagnosis
Lymphocytic Interstitial Pneumonitis
Can occur in patients with HIV
LIP can range from follicular bronchitis
to indolent lymphoma
 Bronchiolitis

Idiopathic
Organizing fibrosis in bronchioles
Cigarette smoke settling on
respiratory bronchioles and setting
up inflammation and fibrosis
Seen with 30 pack year history
 Sarcoidosis -
In the lung - restrictive disease
Multisystem involvement,
noncaseating epitheloid
granulomas
Differentiate from Tb, berylliosis,
fungal infections
Cell mediated hypersensitivity to
some unidentified antigen
 Case history
43 yr old female with bilateral nodular
infiltrates
Hilar adenopathy noted
 Sarcoidosis
Lymph nodes, lungs, skin, eye,
spleen, liver etc
Asteroid bodies, Schaumann bodies
- suggestive but not diagnostic
 Sarcoidosis
May be associated with
hypercalcemia (activation of vit. D
by epitheloid cells)
Raised serum angiotensin
converting enzyme (ACE) - 60%
 Sarcoidosis
Mikulicz Syndrome - Parotid,
sublingual, submaxillary, Uveal
Bilateral uniform enlargement
Sarcoid, lymphoma-leukemia,
Sjogrens syndrome
 Hypersensitivity pneumonitis
Allergic alveolitis (not bronchioles)
Granulomas in alveolar walls, less
fibrosis
Acute (type III) or Chronic (type IV)
Irritation, complement, immune
complex damage
Farmers lung (hay), Bagassosis (sugar
cane), Pigeon breeders lung etc.
 Hypersensitivity lesions
Size of particles
Hay fever (type I)
Bronchitis / asthma
Bronchiolitis obliterans
Pneumonitis (type III,IV)
 Diffuse pulmonary hemorrhage

(Good Pastures Syndrome)

Lung hemorrhage + acute
glomerulonephritis
Antibody to basement membrane
(linear immunofluoroscence)- type II
Hemoptysis + nephritic illness
Triad- hemoptysis, anemia, diffuse
pulmonary infiltrates
 Good Pastures syndrome

Oliguria, hematuria, hypertension

Progressive dyspnea, right heart
failure
Treat by plasmapheresis,
immunosuppression
 Idiopathic pulmonary hemosiderosis

Younger patients
Cause not known - no antibodies, no
renal involvement
Recurrent hemorrhage, fibrosis
 Pneumoconiosis
(Revise environmental pathology)
Anthracosis, silicosis, asbestosis,
berylliosis, Popcorn Lung ->
Restrictive lung disease
Other causes of interstitial fibrosis

Anticancer drugs- busulfan,

methotrexate, cyclophosphamide
Paraquat (herbicide)
Radiation pneumonitis
Toxic gases
Intravenous heroin (contaminants)
Other causes of Interstitial fibrosis

Autimmune disorders- SLE, rheumatoid

arthritis, scleroderma
Wegener's granulomatosis- pulmonary
angitis and granulomatosis-
sinusitis, lung involvement, kidney
involvement, c-ANCA
Chronic obstructive pulmonary
disease
(COPD, COAD)
 COPD
Chronic obstruction to flow of air
Common disease; 4th leading cause of deaths in
the US; 3rd most common cause of death
worldwide by 2020
Once principally a disease of men, it now affects
men and women equally
In 2000, COPD was responsible for 8 million
physician office visits, 1.5 million emergency
department visits, and 726,000 hospitalizations
(about 13% of total hospitalizations)
Second only to coronary heart disease as a reason
for payment of Social Security disability benefits.
 NEJM March 2009
Case Vignette
A 61-year-old woman is referred for pulmonary
consultation.
She smoked one pack of cigarettes a day for 45 years
but quit a year ago.
For 2 years she has noted progressive exertional
dyspnea, with breathlessness occurring when she is
walking up one flight of stairs or hurrying on level
ground.
A diagnosis of chronic obstructive pulmonary disease
(COPD) was made a year ago, and she was treated
with inhaled medications.
Casaburi R, ZuWallack R. N Engl J Med 2009;360:1329-1335
 She is sedentary and recently gained 15 lb
(6.8 kg); her only frequent social activity is
playing cards.
Her physical examination is normal except for
a weight of 195 lb (88.5 kg) (body-mass index
[the weight in kilograms divided by the square
of the height in meters], 32) and for
decreased breath sounds and prolonged
expiration on chest auscultation.
Spirometry reveals moderate airway
obstruction; an echocardiogram is normal.
 What is the Treatment in
2009?
The pulmonary consultant
recommends enrollment in
a pulmonary rehabilitation
program.
 Recommendations
Outpatient hospital based exercise program
of 8 weeks, 3 hour sessions 3 times a week
Pre-exercise, stress test
Relatively high-intensity treadmill, stationery
style ergometer training and low intensity
calisthenics
Maintainence exercise program and COPD
support group
Why Exercise?

Megha Joshi S. Bhusnurmath- 129

Lung Pathology-4-SGUSOM
 Exercise intolerance resulting from dyspnea
or fatigue is often the chief symptom reported
by patients with COPD.
The degree of exercise intolerance roughly
parallels the severity of the disease, but
exercise intolerance is also distinctly present
in patients with only mild disease.
The extent to which quality of life is impaired
is reflected in patients' symptoms, decreased
functional status, and frequency of
exacerbations.
 Pathophysiology
Extrapulmonary effects
Skeletal muscle dysfunction (legs)
Low type 1 fibres; early onset of
lactic acidosis
Fatigue leads to decreased
ambulation rather than dyspnea
 Effects of therapy
Pulmonary rehab doesnt improve lungs
Optimizes function of the rest of the
body
Effect of lung dysfunction on the rest of
the body is minimized
Decreased lactic acidosis, decreased
ventilatory demand
 Obstructive lung disease
Reversible- Bronchial asthma
Irreversible- Chronic bronchitis,
emphysema, bronchiectasis
 Obstructive lung disease
Total lung capacity (TLC)- increased
Forced vital capacity(FVC)- Normal
or decreased
FEV-1 reduced
So FEV1 : FVC ratio reduced (<75%)
 Obstructive vs Restrictive
FEV1 :FEV < 70%

<70%
COPD
 Chronic Obstructive
Pulmonary Disease-COPD
Emphysema and Chronic bronchitis
are the two main conditions
causing COPD
Definition of Emphysema is based on
morphological changes that occur
and the definition of Chronic
bronchitis is based on clinical
features
 Emphysema
Permanent enlargement and destruction
of airspaces beyond terminal bronchioles
( not just overinflation )
There is no real obstruction for a long time
after the disease starts and hence no
symptoms develop.
When symptoms develop it means
obstruction has occurred.
 Emphysema
Permanent dilation of terminal air
spaces with destruction of their
wall.
Elasticity lost, cannot recoil to expel
air
(Inspiration is active, expiration is
passive).
 Emphysema
Elderly males and females with
dyspnea (after significant damage).
No organic obstruction - only failure
of recoil.
May develop chronic bronchitis in
addition.
 Emphysema-Types
1 Centriacinar ( Centrilobular)
2 Panacinar ( Panlobular)

Distinction possible in early stages

and not in late stages.
 Types of emphysema

Normal

Panacinar

Centriacinar

Septal
Megha Joshi S. Bhusnurmath- 142
 Centrilobular emphysema
Damage is at respiratory bronchioles
(central and proximal part of
acinus)
Distal alveoli spared,
Common in upper lobes (apex)
Occurs in Smokers, Smog filled city
dwellers
 Panacinar emphysema
Uniform enlargement from respiratory
bronchioles, alveolar ducts and
alveoli,
Common in lower lobes.
Seen in A1 AT deficiency
 Septal emphysema
Rare variety (distal
acinar)
Next to scars
May form bullae
Chances of
pneumothorax
Pathogenesis of emphysema
 Genetics and COPD
The ADAM33, a disintegrin and metallo-
proteinase gene, has been shown to be
associated with asthma and bronchial
hyper-responsiveness.
This relationship, however, has not
been investigated in tobacco smokers
who are susceptible to COPD.
Only 25 % of smokers get COPD
March 12, 2009 BMC Journal
Researchers from the Wake Forest
School of Medicine, NC, genotyped 880
long-term heavy smokers for 25 single
nucleotide polymorphisms (SNPs) in
ADAM33.
287of the study subjects had COPD and
311 did not.
All of them were older than age 50 years
and all had a cigarette smoking history
of at least 20 pack-years.
March 12, 2009 BMC Journal
Identified five SNPs in ADAM33 that occurred
more frequently in the COPD group than in
the group of smokers without COPD.
All five SNPs (Q-1, S1, S2, V-1 and V4) were
associated with COPD, and the S1
polymorphism had the strongest degree of
association with COPD
The investigators say functional studies are
needed to "evaluate the biologic significance
of these polymorphisms in the pathogenesis
of COPD."
 Pathogenesis of emphysema

Excessive protease (Elastase) + less

anti protease
1. Alpha -1- antitrypsin deficiency
(2% of all emphysema)
Pi MM normal, Pi ZZ worst
2. Neutrophils release elastase
(e.g. cigarette smoking)
 Cigarette smoking
Cigarette smoke particles lodge at
bifurcation of respiratory
bronchioles
Engulfed by macrophages which
release elastase
This elastase is not inhibited by
A1AT and can digest the A1AT
 Cigarette smoking
Cigarette smoke also contains
oxidants
These oxidants along with free oxy
radicals released by pmn.s inhibit
A1AT
 Pathology of emphysema
Panacinar - Large, pale,voluminous
lungs, cover the heart
Centriacinar no changes on X-Ray
- clinically no symptoms
till advanced stage
Micro: alveoli large, wall
thin, destroyed
 Pathology of emphysema
terminal and respiratory bronchioles
deformed
loss of tethering by surrounding
alveoli leads to obstruction in
expiration
 Emphysema- Clinical
Symptoms appear late
Barrel chest, dyspnea, prolonged
expiration
X- ray flat domes of diaphragm
Hyperventilation blood gases normal till
late
Pink Puffers,
Late stage - hypoxia, respiratory
acidosis
 Emphysema
Usually the patients are weak and
skinny
Weight loss because of excess
puffing and panting due to hyper
ventilation
 Emphysema- Clinical

Hypoxia and hypercapnia

Pulmonary vasoconstriction,
compensatory polycythemia
Loss of pulmonary capillary surface
area from alveolar destruction
Pulmonary hypertension
Cor pulmonale ( RVH, RVD,RVF )
 Death in emphysema
Respiratory failure - acidosis,
hypoxia, coma
or
Cor pulmonale
 Other types of emphysema
Congenital
Compensatory : eg. Pneumonectomy
Interstitial Emphysema
Bullous Emphysema
Obstructive overinflation : tumor,
foreign body-- danger of collapse
of rest of lung, pneumothorax due
to rupture
 Mediastinal emphysema
Air escapes in to the connective tissue of
lung stroma, mediastinum and
subcutaneous tissue
Sudden increase in intra alveolar
pressure
violent cough, vomiting, whooping cough,
trauma usually with some obstruction to
the bronchial passage- eg mucus plug
tear in the interstitium
 Mediastinal emphysema
Patient bloats suddenly like a balloon
including chest head and neck
Crackling crepitations over chest
wall
Recovers spontaneously after the
defect is sealed
 Chronic bronchitis
Cigarette smokers, smoke in city
Persistent productive cough for at
least 3 consecutive months in at
least 2 consecutive years.
Types: Simple, mucopurulent,
asthmatic, obstructive
Chronic bronchitis
 Pathogenesis
Irritation Excess secretion by mucus
glands hypertrophy of glands
Metaplastic goblet cells in surface
epithelium, secondary bacterial
infection (ciliary dysfunction)
Inflammation and fibrosis obstruction
of small airways (Bronchiolitis obliterans)
Superimposed emphysema.
 Pathology
Externally lungs appear normal
Large airways - hyperemia, edema,
mucous secretion
Reid index
Chronic bronchitis - bronchi
hypertrophy and hyperplasia of
mucous glands
(Reid Index > 0.5); Normal 0.4
Increased goblet cells in the surface
epithelium
Squamous metaplasia
Chronic bronchitis - bronchioles

Goblet cell metaplasia

Inflammation
fibrosis (collapse in expiration)
smooth muscle hyperplasia
 Chronic bronchitis - Clinical
Definition
Eventually small airways obstruction
pO2, pCO2, Cyanosis
Blue bloaters (edema due to heart
failure)
Pulmonary hypertension, Cor
pulmonale
Secondary infections
Pulmonary hypertension
 Chronic bronchitis
Persistent hypercapnia makes
respiratory centers insensitive to
pCO2 stimulus
Respiration is now driven by low O2
If you administer oxygen the drive
is lost and they die of CO2 narcosis
 Bronchial asthma
Sudden attacks of respiratory
distress
Dyspnea
Wheezing / Rhonchi
Episodic
Relieved spontaneously or by
bronchodilators
Thick sputum
 Bronchial Asthma
Hypersensitivity of tracheobronchial
tree
Bronchiolar smooth muscle spasm
Bronchial inflammation precipitates
the hyper reaction of bronchial
tree
Bronchial inflammation is now
considered the important feature
 Types of asthma
Intrinsic
Extrinsic

Final mechanism of damage similar

and hence the distinction may not
be that relevant
 Intrinsic
Non-immune mechanism
Viral infection
Cold
Asthmatic bronchitis in Smokers
Exercise induced
Drug induced, aspirin
 Extrinsic (Atopy)
(Type I hypersensitivity; exposure to
an extrinsic antigen)
Childhood, familial, serum IgE,
sensitivity to many antigens
Raised eosinophils in blood
Older patients serum IgE normal
 Other types
Allergic bronchopulmonary
aspergillosis
Occupational Asthma
Bronchial asthma - mechanism-1
increased TH-2; decreased TH-1
Absence of T-bet
Bronchial asthma

Megha Joshi S. Bhusnurmath- 179

 Genesis
CD4 cells of Th2 subtype release IL
4,5,13
These favor synthesis of IgE, growth
of mast cells and growth and
activation of eosinophils
 Genesis early phase
Early Phase starts in 30-60 minutes of
exposure and lasts up to 4-6 hours
Antigen + IgE on mast cells in
mucosa
Release Histamine, bradykinin,
Leukotreines, Prostaglandins,
platelet activating factors
Bronchoconstriction, acute
inflammation, thick mucus
 Genesis early phase
Epithelial damage
Opens the intercellular junctions
Antigens get in
Sensitize mast cells in submucosa
Aggravation of reaction
Stimulation of submucosal vagal
fibers leads to reflex smooth
muscle contraction
 Genesis late phase
Starts after 4-6
hours
Eosinophils play
the dominant role
 Eosinophils
Eosinophils attracted by IL5, PAF
(mast cells), eotaxin (epithelial
cells)
Amplify and sustain the reaction.
Recruitment of pmn.s, basophils,
eosinophils, CD4 cells
 Eosinophils
Have granules like mast cells
The granules contain eosinophil
cationic protein and major basic
protein which are toxic to
epithelial cells
 Late phase
Epithelial cells secrete- endothelin
and Eotaxin
Lead to smooth muscle contraction
 Late phase
Eosinophils produce Leukotreines
C4,PAF activate mast cells
Cytokines activate myofibroblasts to
lay down more collagen in the
basement membrane
 Genetics
Microenvironment of bronchial tree-
altered due to genetic mutations in
metalloproteinases- ADAM-33
This precedes the development of
asthmatic attacks and may
predispose to it
 Effects of Asthma
Obstruction, more in expiration
(wheeze)
FEV-I < 30%, hyperventilation
Hypoxia, hypercapnia, respiratory
acidosis
 Asthma - lungs
Occlusion of bronchi, bronchioles by
thick tenacious mucus
Overinflated lungs
 Asthma lungs- micro
Eosinophils, mucus plugs in lumen
Inflammation- eosinophils, mast
cells, basophils, macrophages,
CD4 lymphocytes, neutrophils
Edema
 Asthma lungs- micro
Thick basement membrane
Patchy necrosis and shedding of
epithelial cells
Hypertrophy of submucosal glands
and increase in goblet cells in
bronchial lining
Hypertrophy of smooth muscle
 Asthma - Clinical
Short, acute attacks - Expiratory
dyspnea, wheeze, dry cough
Thick stringy mucus, casts,
(Curschmans spirals; epithelial
casts)
Charcot Leyden crystals; crystalloids
made up of eosinophilic membrane
protein
 Asthma - Clinical
Respond to bronchodilators
Skin tests - desensitize
Status asthmaticus (severe,
prolonged)
 Asthma - management
Acute attacks-
bronchodilators
Steroid inhalers (anti-inflammatory)
Antihistamines
Leucotrine blockers ( Accolate)
Prevention , Desensitization
 Bronchiectasis
Permanent, abnormal, irreversible
dilatation of bronchial tree
proximal to terminal bronchioles
Result of chronic infection
destruction, fibrosis, dilatation.
 Associated with
Obstruction - tumors, foreign bodies
Congenital-- Cystic fibrosis,
Kartageners syndrome,
Post infectious states--Necrotizing
bronchopneumonia--TB, Staph,
Pseudomonas, viruses,
(Sequela to measles,Whooping cough)
Other-- RA, SLE, IBD
 Kartageners syndrome
Bronchiectasis, sinusitis, situs
inversus, Kartageners syndrome
Lack of ciliary activity
upper respiratory infections +
sterility in male + Dextrocardia
Loss of cell motility during
embryogenesis
 Dynein arms
short or absent or smile!
Pathology of bronchiectasis
Localized or generalized
Cylindrical, fusiform or saccular
Bronchi reach up to pleura
Walls inflamed, fibrosed, ulcerated,
purulent
Lung abscess
 Bronchiectasis - Clinical
Productive cough
Large amount foul sputum
Episodic fever
Clubbing of fingers
Pulmonary hypertension, Cor
pulmonale
Amyloidosis
Neoplasms
 Lung tumors
Primary
Originating in the Lung
Secondary
Metastases
Origin of tumor elsewhere, but now
involving and spread to lung
 Carcinomas
Adenocarcinomas 10
Squamous 4
Mixed 2
Large Cell 1
Small Cell 1
Carcinoid tumor 1
Mesothelioma 1
 35 year old Female with
bilateral interstitial lung
disease
Diagnosis: Langerhans Cell
Histiocytosis
 63 year old female with 2
nodules in left lung
Diagnosis: Small Cell Carcinoma
67 year old female with mass
in right lobe
Diagnosis: Squamous Cell Carcinoma
81 year old female with known
history of colon cancer
presents with left upper lobe
lung mass
Diagnosis: Adenocarcinoma
(bronchioalveolar type)
 70 year old woman with
carcinoma in right lung
Diagnosis: Adenocarcinoma
 81 year old female presents
with a left lung tumor
Diagnosis: Bronchial Carcinoid
44 year old male with a history
of thyroid carcinoma presents
with tumor in right lobe
Diagnosis: Large Cell Carcinoma
 53 year old female with a
carcinoma of the lung
Diagnosis: Non Small Cell Carcinoma
(large cell)
 60 year old male with a
carcinoma of the right upper
lobe
Diagnosis: Adenocarcinoma, with
bronchioalveolar, acinar, and solid
areas
 Primary
Bronchial epithelium - 95%
5% Carcinoid, mesotheliomas,
bronchial gland, mesenchyme,
lymphoma
 Bronchogenic carcinoma
No. 1 cause of cancer deaths in the
U.S.
No. 1 cause of cancer deaths in
females also
Cigarettes smoking : 10 times more
common in smokers
40 - 70 years peak age group; 2% of
all cases occur before age 40
 Lung Cancer
Outlook for patients diagnosed with
lung cancer is dismal
1-yr relative survival rate 41%
5- yr rate for all stages combined is
15%
No good screening test available
Many present with Stage IV and
metastases
 Etiogenesis
Tobacco
Air Pollution: atmospheric pollution and
indoor pollution (high radon in soil)
Industrial Hazards: ionizing radiation,
uranium miners, asbestos (1 in 5 deaths
due to lung CA)
Familial clustering and genetic
predisposition
P450 polymorphisms, mutagen sensitive
phenotype
Molecular genetics:
Oncogenes c-MYC, K-RAS, EGF-R, Her-2/neu
Tumor suppressor genes p53, RB, p16 and 3p
del
 Classification
1. NSCLC - Non Small Cell Lung
Carcinoma (70-75%)
Squamous Cell Carcinoma (25- 30%)
Adeno Carcinoma (30- 35%)
Large Cell Carcinoma (10-15%)
2. SCLC - Small Cell Lung Carcinoma
(20-25%)
3. Large cell Neuro-endocrine Carcinoma
4. Mixed Cell Types; Adeno squamous,
Small cell and non-small cell types
 Smoking and lung cancer
evidences
STATISTICAL - Pack years -
90% of carcinomas arise in smokers
Heavy Smokers vs Nonsmokers- 60
times (>40 cigarettes/day for many yrs)
15 years after stopping smoking - risk
reduced, never reaches normal
Passive smoking (x2)
3000 die/yr from second hand smoke
 Smoking and lung cancer
Tobacco smoking causes 90% of all lung
cancers, but only
10-20% of smokers get lung cancer
Getting cancer from smoking is really a
stroke of Bad Luck for the smoker
For the fully invasive malignant phenotype
to develop, closer to 12 critical genetic
alterations are required; in the correct
order
Only 10-20% of smokers achieve full set of
changes in a single clone
 Smoking and lung cancer
4000 chemicals identifiable in cigarette smoke
50 recognized as carcinogens by FDA
Most closely studied are polycyclic aromatic
hydrocarbons (PAHs) and N-nitrosamines(NNK)
Procarcinogens in cigarette smoke are converted
into carcinogens by host xenobiotic metabolizing
enzymes (XMEs) like P450s, CYPs
Enzymes like Glutathione S Transferase convert
toxic compounds into less toxic ones
These enzymes are variable in their prevalence and
efficacy
 Smoking and Cancer
High risk CPY polymorphisms and p 53
mutations seen with Squamous cell
carcinoma
Glutathion S transferase and K RAS
mutations seen with adenocarcinoma
ERCC1 polymorphisms linked to small cell
carcinomas
Mutagen sensitive phenotype risk x10
Greater addiction to nicotine due to
polymorphisms in the nicotine receptor
gene
 Genetic Predisposition to
Lung Cancer
Familial clustering
Cytochrome P mutations, lead to
rapid conversion of procarcinogens
to carcinogens
Higher incidence of
adenocarcinomas in females, many
without a history of smoking
 Lung carcinogensis
pathways
Epithelial changes in sequence
Central bronchial epithelium--squamous
dysplasia--Ca in situ--SCC and Small Cell
carcinoma
Terminal respiratory unit epithelium--Atypical
Adenomatous Hyperplasia--Bronchoalveolar
Carcinoma--AdenoCA
Diffuse idiopathic pulmonary neuroendocrine
hyperplasia
EXPERIMENTAL - Missing link
 General features
Majority HILAR
Smoking - special relation to
Squamous cell, Small cell
Aggressive infiltration
Metastasis: Liver, Adrenal, brain,
bones, kidneys
Paraneoplastic Syndrome (specially
SCLC)
 Squamous cell carcinoma
Male > female
Central (hilar) location
Hilar lymph nodes
Cumulative pre cancerous histologic
changes
Obstruction, atelectasis, infection
 Adenocarcinoma
Younger age < 40 years
Women, Non smokers
Peripheral (coin lesion)
May relate to scars (infarct,
granuloma, TB, diffuse fibrosis)
Scar carcinomachronic scarring
leading to carcinoma
 Adenocarcinoma
AAH- atypical adenomatous
hyperplasia
? Precursor of adenocarcinoma
Is there a spectrum from AAH-
bronchoalveolar carcinoma to
frank adenocarcinoma?
 Distinguish from scar caused by
cancer
Slow growth
Early metastasis
Types: acinar, solid, papillary,
broncho-alveolar, mucin forming,
mixed
Bronchiolo alveolar carcinoma
Multiple coalescing nodules - pneumonia
like, alveolar growth pattern
Kill by suffocation
Tall columnar cells with mucin
EM shows surfactant producing type II
pneumocytes, Clara cell or mucin
secreting bronchiolar cells
(South African sheep - infection -
Jagziekte shows similar features)
 Large Cell Carcinomas
Squamous or Adeno
with no differentiation
Poor prognosis, early
metastasis
 Small Cell Carcinomas
Male > females
Related to Smoking
Hilar location
Cells resemble lymphocytes
Frequent mitosis
Molding, inconspicuous nucleoli
 Small cell carcinoma
Frequent vascular invasion
Infiltrate and metastasize widely
Not resectable
Responsive to chemotherapy
Neuro endocrine origins
(Paraneoplastic Syndromes)
 Small cell carcinoma
Immunohistochemistry:
Chromogranin, Synaptophysin, CD
56, TTF -1, positive
EM dense neurosecretory granules
Ectopic hormone secretion:ACTH,
ADH, Calcitonin, Gastrin Releasing
Polypeptide etc.
 Spread of lung cancer
Infiltration lung, pleura, pericardium,
Superior vena cava (SVC), Cervical
sympathetic plexus,
Lymph nodes (Carina Mediastinal,
Scalene, Supra clavicular)
Virchows LN
Liver(30-50%), adrenal (50%), brain
(20%), bone (20%)
 Staging of lung cancer
TNM classification
T1<3cm, T2>3cm, T3 chest wall, T4
mediastinum
N1 ipsilateral hilar and bronchial LN
N2 ipsilateral mediastinal, subcarinal
N3 contralateral mediastinal or hilar
M0 No known distant metastasis
M1 Distant metastasis
Only 15% lung cancers are detected in
early stage (localized)
 TNM classification, 2009
IASLC (International Association for the
Study of Lung Cancer)
Studied >100,000 lung cancer cases
White paper
T1 further divided: <2, 2-3
T2 further divided: 5, 5-7
M categories also changed
 Clinical features
Peripheral- may be clinically silent
Hilar (Central)-
Obstruction- partial or total
Infection- pneumonia, abscess,
bronchiectasis
Atelectasis
 Clinical features
Cough, weight loss, hemoptysis,
dyspnea
Pulmonary osteoarthropathy -
(clubbing)
Hoarseness (recurrent laryngeal
nerve involved), chest pain
Pericardial and pleural effusion
 Clinical features
Persistent atelectasis, pneumonitis
(obstruction)
Superior vena cava (SVC) syndrome
due to obstruction
Horners Syndrome: Cervical
sympathetic plexus damaged
Ipsilateral enophthalmos, ptosis,
meiosis, anhidrosis
 Clinical features
Pancoasts tumors (apical neoplasm) T1T2
destruction
wasting of hand muscles, pain in arms
Horner syndrome
Recurrent laryngeal nerve paralysis
Esophagus involvement
dysphagia
Thoracic duct obstruction
chylothorax
Clinical features- metastasis
LN mets most common
Adrenal (50%)-very rarely
Addisons (insufficiency)
Liver (30-50%) hepatomegaly
Brain (20%) mental, neurologic
Bone (15-20%) Pain, fracture
Kidney- (15%)
 Prognosis in lung cancer
SCLC carries worst prognosis
Usually metastasis by the time of
detection
Median survival l year
Chemotherapy for SCLC
Lobectomy or pneumonectomy for
NSCLC if localized
 Paraneoplastic syndromes
10% of all lung cancers (SCLC)
Hypercalcemia (PTH)- more with
squamous cell carcinomas
Cushings (ACTH) bilateral adrenal
hyperplasia
Syndrome of inappropriate
ADH secretion Hyponatremia
Gonadotropins - gynecomastia
 Paraneoplastic syndromes
Neuropathy, myopathy
Clubbed fingers, hypertrophic
pulmonary osteoarthropathy
Migratory thrombophlebitis
DIC, nonbacterial thrombotic
endocarditis (NBTE) more
common with adenocarcinoma
 Carcinoid tumor
Cells look like carcinoma cells but
are not truly carcinoma cells
because they do not arise from
epithelial cells
Arise from Neuroendocrine
(Kulchitsky) cells
 Carcinoid tumor
Neuroendocrine cells
Part of a widespread system
Neuro secretory granules seen in the
cytoplasm
? Precursor lesion in the form of local or
diffuse neuroendocrine hyperplasia
? Carcinoid tumor is a precursor for Small
cell carcinoma
 Carcinoid tumor
Usually localized
Located in the main bronchi (Hilar)
Resectable
Age group of 40 years
 Carcinoid tumor
Growth Polypoid,may grow in and
out of bronchial wall- collar button
Micro:- uniform round cells in nests,
no pleomorphism or mitosis
Nuclei not hyperchromatic
 Carcinoid tumor- death
Pneumonia
Lung abscess
Bleeding
 Carcinoid tumor - clinical
Obstruction - cough, hemoptysis,
infections (Hilar location)
May be incidentally detected
Carcinoid Syndrome may be
produced
Good Prognosis- usually benign
Rare metastasis
 Carcinoid syndrome
1% of all Carcinoid tumor patients
show carcinoid syndrome
Symptoms due to high 5HT, 5HIAA in
blood and urine (produced by the
tumor cells)
Others may be histamine, bradykinin,
prostaglandins
 Carcinoid Syndrome-
Features
Episodic attacks
Vasomotor
disturbances(flush
es, cyanosis)
GIT hyper
motility(diarrhea,
cramps, vomiting)
Asthma attacks
 Carcinoid tumor
Lung carcinoids secrete into
systemic circulation (produce
symptoms of the syndrome)
Carcinoid tumors occur in the gut
also
 Carcinoid syndrome
Gut carcinoids secrete into portal
circulation Liver metabolizes
the secretions (no symptoms)
If metastasis to liver from gut
carcinoids - secretions from the
tumor cells in the liver get into
circulation - carcinoid syndrome
produced
 Systemic fibrosis
Heart involvement
gut carcinoids - right ventricle
endocardium, pulmonary and tricuspid
valve ;
bronchial carcinoids -
Left ventricle
Retroperitoneal fibrosis
 Hamartoma - Lung
Made up of cartilage, blood vessels,
fat, spaces lined by bronchial
epithelium
Silent clinically, picked up
incidentally by X- ray
Peripheral location- Coin lesion
Resection cures it
 Coin Lesions
Peripheral nodular lesion picked by
by X-ray chest
peripheral adenocarcinoma
hamartoma
inflammation
FNAC to make a diagnosis
 Mesothelioma
Asbestos (shipyards, miners,
insulators)
25 - 40 years
Asbestos + Smoking Increased
bronchogenic carcinoma not
increased risk for mesothelioma
Amphibole variety not serpentine
 Mesothelioma
Fibers stay in the body for life
Preceded by - Extensive pleural
fibrosis, plaque formation
Pleural effusion, spread along pleura
Yellowish firm gelatinous
encasement
Obliterates pleural space
 Mesothelioma
Metastasis rare but infiltrates lungs
and thoracic wall
Micro: Combination of epithelial
(adenocarcinoma) and connective
tissue (sarcoma) elements
Nasopharyngeal carcinoma
Common in Chinese (? Genetic)
EBV - genome in all of them
Occult primary-usually presents as
metastatic lymph nodes in the
neck
Nasopharyngeal carcinoma
Squamous cell carcinoma
Poorly differentiated carcinoma
(EBV)
Lympho epitheliomas
radiosensitive
 Carcinoma larynx
M: F 7:1
Smoking, alcohol, asbestos
Squamous cell carcinoma
Intrinsic, Extrinsic (extended outside
larynx)
 Carcinoma larynx
Clinical: Hoarseness, pain,
dysphagia, hemoptysis
Infection of lung
60% localized resect
Investigations for lung cancer

Sputum (can detect overt and occult

cancer)
X-ray, CT
Pleural fluid tap
Pleural biopsy
Investigations for lung cancer

Bronchoscopy
Bronchoscopic cytology, biopsy
Bronchoalveolar lavage
 Investigations for lung cancer

Ultrasound / CT guided FNAC

Open lung biopsy
Lymph node, liver FNAC
Hormonal assay- ( paraneoplastic
syndrome )