Pathophysiology Lecture 10

Topic: Pulmonary Function

Tests
Dr. S. Upadhya

1
 Learning Objectives: Pulmonology

Compare and contrast the respiratory disorders listed in the

next slide with reference to:
• Risk factors
• Etiology and pathogenic mechanism
• Altered morphology, physiology
• Signs and symptoms and basis for signs and symptoms
• Differential diagnosis
• Nutritional factors/aspects involved in the disease/disorder
• Prognosis, complications, mortality/survival
• Investigations (screening and confirmatory- list principles
involved and results expected)

2
 List of respiratory disorders to be
covered in lectures and DLAs

• Chronic Obstructive Pulm Diseases

• Interstitial/Infiltrative Lung Diseases
• Respiratory Failure
• Pneumonias & Tuberculosis
• Lung Cancers
• Pleural diseases
• Pulmonary Vascular diseases
Lecture topics are in black; DLA topics are in blue.
3
 Please study ALL DLAs of
Pulmonology posted in sakai before
the IMCQ session on this module
Pulmonary Function Tests (PFTs)
Types of Pulmonary Function Tests

• Tests of ventilatory capacity (Spirometry)

• Lung volume determination
• Measurement of diffusing capacity of
lung (DL)
• Tests of respiratory muscle strength
Maximal Respiratory Pressures)
• Measurement of gas exchange (ABGs)

6
Sample PFT data sheet

7
 Spirometry
• The best tests of pulmonary function.
• Measurement of ventilatory capacity by forced
volume exhaled & Forced volume exhaled/time.
• The most relevant measurements are:
– Forced Vital Capacity (FVC in Liter)
– Forced Expiratory Volume in the first second
(FEV1 in Liter)
– FEV1/FVC ratio (in percentage)
– Flow-volume curve
– Peak Expiratory Flow Rate (PEFR in L/minute).
8
 Normal Spirometry

FVC > 80% Predicted

FEV1 > 80% Predicted
FEF 25-75% > 65% Predicted

9
Spirometry: Forced Volume-Time curve

6
Normal
5

Forced Vital Capacity

(FVC)
4

Volume (L) 3

Forced Expired
Volume in 1 second FEV1/ FVC >0.70
2
(FEV1)

0
0 1 2 3 4 5 6 7 8

Time (sec)
10
 Forced Volume-Time curve: Patterns in
Diseases

6 6

5 5
Normal
4 FVC Normal
4 FVC
Volume (L)

FEV1 Mild obstruction FEV1 Restriction FEV1/ FVC>0.70

Volume (L)
3 FVC
FEV1
3 FEV1
FVC
Severe obstruction
2
2
FEV1/FVC=1.00
FEV1
FEV1/ FVC
1
= 0.44 1

0
0
0 1 2 3 4 5 6 7 8
0 1 2 3 4 5 6 7 8
Time (sec)
Time (sec)

11
Flow-Volume curve: Characteristics of correct
spirometry

Residual volume (RV)

FVC=TLC-RV
TLC

RV

12
 Flow-Volume Curve: Measurements
6

5
Normal PEFR: 250 – 700 Liter per min

4
Peak Expiratory Flow (PEFR)

3
Flow (L/s)

Normal curve FEV1/ FVC >0.70

2

1
Forced Vital Capacity (FVC)
RV
0
0 1 2 3 4 5 6 7 8

TLC Volume (L)

13
 Flow-Volume curve: Forced Expiratory
Flow (FEF) calculation

FEF 25% FEF50%: Forced expired flow

at 50% of vital capacity
FEF 50%

+
FEF 75%

Flow Volume (Liters)

1 2 3 4
_
FEF25-75%: Forced expired flow
Between 25% & 75% of vital capacity
14
 Flow Volume curve in Mild
Obstruction (Red curve)

“Scooping” of the
expiratory loop
+

Flow Volume (Liters)

1 2 3 4
_

15
 Flow-volume curves in different conditions
Flow (L/sec)

Volume (Liters)
Note: By convention, lung volume increases to the left on the abscissa.
16
Sample PFT data sheet

17
Sample PFT data sheet

18
Spirometry: Peak Flow Meter

• Measures highest flow sustained

for 10 msec
– expressed in L/minute
• Correlates well with FEV1
• Variability (%) = [(high - low)/high] x100
– ideal daily variation <10-20% in
stable situation
– for use in asthma.

19
 Lung Volumes and Capacities

Residual volume can not be measured by a simple spirometer.

20
Sample PFT data sheet

21
Measuring FRC: Helium (He) dilution technique
V1 V1+FRC

C1 C2

V1xC1 = (V1+FRC)xC2 (since the amount of He is the same)

22
Measuring FRC: Using Body Plethysmography

FRC is measured by
relating volume changes
to pressure changes in
a rigid compartment
23
Lung Volumes/Capacities in Resp.
Diseases

24
Diffusing Capacity (DL) or Transfer Factor (TF)

• Conductance term.
• Volume of gas diffused
through the alveolo-
capillary membrane per
minute per mmHg
pressure gradient.
• Determined by using
Carbon monoxide (CO).
• Measured in mL/mmHg/min.

25
Diffusing Capacity: Factors that cause of
a low value
• Reduced or lost alveolar
surface area
• Reduced or lost capillary
surface area
• Increased diffusion
distance

26
Sample PFT data sheet

27
Measurement of Maximal Respiratory
Pressures

• Maximal Inspiratory Pressure (PImax)

– global inspiratory muscle strength
– mainly diaphragm.

• Maximal Expiratory Pressure (PEmax)

– global expiratory muscle strength
– mainly abdominal muscles.

28
Sample PFT data sheet

29
Arterial blood gases (ABG): what is
measured?

• Arterial pH
• Arterial PO2 (PaO2)
• Arterial PCO2 (PaCO2)
• Arterial Bicarbonate (HCO3)
• Hemoglobin concentration (Hb)
• Oxygen saturation of Hb (SaO2)

30
Sample PFT data sheet

31
Arterial blood gases: What do they inform?

• Hypoxemia (Low PaO2)

• Hypercapnia (High PaCO2)
• Both

32
 Causes of hypoxemia
• Ventilation-Perfusion mismatch

33
 Causes of hypoxemia
• Intrapulmonary shunts OR
right-to-left intracardiac shunts

34
Changes in ABG values in Hypoventilation
• Ventilatory pump failure
• ABG shows Low PaO2; High
PaCO2 and High HCO3
• Respiratory acidosis

35
 Arterial blood gas:
Assessment of CO2 elimination
High PaCO2 indicates:
• Poor ventilatory drive (hypoventilation)
• Abnormal respiratory mechanics
– severe airways obstruction
– weak respiratory muscles
• Severely deranged lung parenchyma causing
VA/Q mismatch

36
Pulse Oximeter: Assessment of oxygenation
Noninvasive method of measuring oxygenation level
in the blood.

Oxygen Saturation as measured by pulse oximeter = SpO2

Oxygen Saturation as measured by ABG = SaO2. 37
Oxygen saturation of Hb: Assessment of
tissue oxygenation

P50 38
Physiological principles of treatment of
Hypoxemia in Resp Failure

• Desirable to
keep PO2 50-
60 mmHg

• Can do this
with a variety of
oxygen devices
Normal Chest X-ray: PA view
40
(Image Provided by EBM Consult)
 HOW TO READ A CHEST X-RAY

•First look at the mediastinal contours, run your eye down the left side of the patient and then up
the right.
•The trachea should be central. The aortic arch (knob) is the first structure on the left, followed
by the major pulmonary artery continues as the left pulmonary artery.
•Two thirds of the heart lies on the left side of the chest, with one third on the right. The heart
should take up no more than half of the thoracic cavity. The left border of the heart is made up
by the left atrium and left ventricle.
•The right border is made up by the right atrium alone. Above the right heart border lies the edge
of the superior vena cava.
•The pulmonary arteries and main bronchi arise at the left and right hila. Enlarged lymph nodes
can also occur here, as can primary tumors. These make the hilum seem bulky - note the
normal size of the hila on this film.
•Now look at the lungs. Apart from the pulmonary vessels (arteries and veins), they should be
black (because they are full of air). Scan both lungs, starting at the apices and working down,
comparing left with right at the same level, just as you would when listening to the chest with
your stethoscope. The lungs extend behind the heart, so look here too. Force your eye to look at
the periphery of the lungs. You should not see many lung markings here; if you do then there
may be disease of the air spaces or interstitium.
•Make sure you can see the surface of the hemidiaphragms curving downwards, and that the
costophrenic and cardiophrenic angles are not blunted - suggesting an effusion. Check there is
no free air under the hemidiaphragm.
•Finally, look at the soft tissues and bones. Are both breast shadows present? Is there a rib
fracture? Are the bones destroyed or sclerotic?
41
Pathophysiology Lecture
11:
Topic: COPD & ASTHMA

DR. S. UPADHYA

1
Patient:
History: A 61-yr-old woman presents with
progressive dyspnea. There is no history of
significant cough or sputum. She smokes two
packages of cigarettes per day for almost 45 years.

Physical examination:
Thin individual in mild respiratory distress at rest.
She breathes with a pursed-lip and a prolonged
expiratory phase. There is no cyanosis, clubbing or
peripheral edema.
Chest auscultation reveals reduced breath sounds.
Chest X-ray: shows hyperlucency.
Pulm Function Tests: Next slide
Diagnosis: Chronic obstructive lung disease. 2
Pulm Function Test Report Radiograph

3
 Obstructive Lung Disease

Disease Entities:
❑ Chronic obstructive pulmonary disease
(COPD) - Emphysema & Chronic bronchitis
❑ Asthma
❑ Miscellaneous - Bronchiolitis, Upper airway
obstruction.

4
Chronic Obstructive Pulmonary Disease

5
 COPD
Definitions
▪ COPD
• chronic, irreversible airflow limitation;
usually progressive
▪ Chronic bronchitis
• cough and sputum for >3 mo/yr
• for >2 yrs
▪ Emphysema
• abnormal, permanent enlargement of
the airspaces distal to the terminal
bronchioles
6
 Emphysema: Pathogenesis

Macrophage elastase aka Matrix metalloproteinase-12 (MMP-12)

7
Emphysema - Pathology
Loss of alveolar units

8
Pathophysiology: Changes in compliance in
Emphysema
•Loss of elasticity leads to less collapsing
tendency of lungs
•Compliance of lungs is increased
•Collapsing tendency of lungs become less than
expanding tendency of chest wall
•These opposing forces are balanced (equilibrium)
at higher resting lung volume
•High FRC and barrel shaped chest

9
Normal Emphysema
 Compliance of Compliance Total
Lung alone (Lung + Chest wall)

FRC

Emphysema: Collapsing tendency of lungs is reduced

Equilibrium occurs at a higher lung volume
10
 Chronic Bronchitis: Clinical Features
(History)

• Typically 40-50 year old

• Insidious onset of cough, mucoid sputum:
Morning only (early disease); eventually continuous
• Smoking history: Minimum smoking exposure of
20 pack-years (1 ppd x 20 yrs)
• Dyspnea: Initially exertional, progressive.

11
 Chronic bronchitis: Pathophysiology
Cigarette smoking & other air pollutants
↓
Inflammation, Hypersecretion of mucus glands and
goblet cells in large and small air ways
↓
Air flow obstruction

Mucus plugging, Coexistent

inflammation & fibrosis emphysema
of bronchiolar walls

Inflammatory cells include macrophages, lymphocytes and neutrophils but

NOT eosinophils. 12
 COPD: Pathology

Combinations of following:
•Inflammation
•Edema of the airway mucosa
•Increased mucus secretion due to
submucosal gland hyperplasia, goblet cell
hyperplasia
•Hypertrophy of smooth muscles
•Mucus-plugging & fibrosis of the small
airways
•Enlarged airspaces due to destruction of
alveolar walls without fibrosis
13
 COPD: Pathology

Normal COPD
14
 Pathophysiology of airway obstruction:
A, B, C

Accumulation Loss of elastic Fibrosis

of inflammatory recoil & and
cells, mucus, destruction of narrowing
and exudate alveolar septa
15
 Pathophysiology of COPD

• Airflow obstruction / airway

narrowing
• Hyperinflation of the lungs
• Gas exchange defects

16
COPD: Alteration in Pulm Function Tests

• Spirometry
• Airflow obstruction: ↓FEV1, ↓FEV1/FVC
• Lung volumes:
• Hyperinflation: ↑ TLC, ↑ FRC
• Air-trapping: ↑ RV & TLC
• Gas exchange
• Mild-mod COPD: Hypoxemia
• Severe (FEV1< 1L): Hypoxemia &
Hypercapnia
• If Emphysema: ↓DLco.
17
COPD: Clinical Features (Physical exam)

• Prolonged expiration,
• Cachexia,
• ↑ Respiratory rate,
• Pursed lips & accessory muscle use,
• ↓ thoracic excursion & barrel chest,
• Hyper-resonant chest percussion,
• Auscultation: Quiet breath sounds, crackles,
wheezes.

18
Forced expiration is harmful in COPD patient

19
Pursed Lip Breathing (PLB): Pathophysiology

Ordinary Pursed lip

breathing breathing
in COPD in COPD

PLB decreases velocity of

air flow and increases the
airway pressure, which
prevents collapse of the non-
cartilagenous airways. 20
Advantages of Pursed-lip breathing:

•Improves ventilation
•Releases trapped air in the lungs
•Keeps the airways open longer and
decreases the work of breathing
•Prolongs exhalation to slow the
breathing rate
•Improves air circulation in the lungs
•Relieves shortness of breath
•Causes general relaxation

21
 COPD: Chest radiography
• Early/mild: normal
• Mod-severe: hyperinflation
▪ low, flat diaphragms
▪ retrosternal airspace
• Emphysema:
▪ hyperlucency
▪↓vascular markings
▪ bullous changes
• Chronic bronchitis
▪↑ bronchovascular markings
22
 Emphysema vs. Chronic Bronchitis
Pink Puffers Blue Bloaters
• No bronchitic • Bronchitic
component component
• Barrel-chest cough, mucus
• Dyspnea early • No barrel chest
• Hunched-over • Dyspnea late
• Hyperventilation
• No air hunger
• Adequate
oxygenation • Ventilation - OK
• Weight loss • Cyanosis
• Cor Pulmonale
• Obese
23
Pink puffer

24
Blue bloater

25
 COPD: Complications

• Gas-exchange abnormalities:
o hypoxemia, hypercapnia, chronic respiratory
acidosis
• Recurrent respiratory infections
• Acute respiratory failure (↑pCO2, ↓pH)
• Barotrauma (pneumothorax)
• Malnutrition (cachexia)
• Cor pulmonale (right heart failure)
• Pulmonary remodeling (chronic)

26
 COPD: Acute Exacerbations

• Mostly Infectious: Viral (common) or

bacterial
• ↑ Dyspnea

• ↑ sputum volume, ↑ viscosity, ↑purulence

• Bacteria: S. pneumonia, H. influenza,

M. catarrhalis

27
Patient:
History:
A 26-year-old student with a history of intermittent
dyspnea presents to the ER with an acute onset of
dyspnea associated with chest tightness, wheezing,
cough and sputum. The attacks typically start by factors
such as inhaling cold air or doing exercise.
Physical examination (during attack):
Moderate respiratory distress at rest. There is no
cyanosis, clubbing or peripheral edema.
Chest auscultation reveals inspiratory and expiratory
wheezes.
Investigations: Next slide
Diagnosis: Bronchial Asthma

28
29
 Asthma
Definition:
• “Asthma is a chronic inflammatory disorder of
the airways in which many cells play a role,
including mast cells and eosinophils.
• “In susceptible individuals, this inflammation
causes symptoms ...
• “... which are usually associated with widespread
but variable airflow obstruction that is often
reversible, either spontaneously or with
treatment ...
• “... and causes an associated increase in
airway responsiveness to a variety of stimuli.”

30
 Asthma: Pathogenesis
Genetic factors
• Family history: atopy, asthma
• Bronchial hyperresponsiveness triggered by
specific allergen

Environmental factors
• Personal smoking
• Environmental tobacco smoke
• Air pollution
• Occupational exposures
• Athletic exposures – cold air, pollution

31
 Asthma Mediators
Mast Cell
Bronchoconstriction
Macrophage
Edema
Epithelial cell Microvascular leak
Eosinophil INFLAMMATORY Exudation
Neutrophil MEDIATORS
Mucus hypersecretion
Platelet

Lymphocyte Bronchial hyperresponsiveness

32
 Most common Asthma Mediators

Histamine
Prostaglandins (D2, F2a, E2 & I2)
Leukotrienes (B4, C4, D4 & E4)
Platelet Activating Factor
Bradykinin
Substance P
Anaphylatoxins

They all cause Bronchoconstriction, Mucus secretion,

Microvascular leak and Chemotaxis
Pathogenesis of Asthma

34
Pathogenesis of Asthma (continued)

35
 Asthma: Airway inflammation
Acute Chronic “remodeling”

•Airway constriction • Subepithelial fibrosis

• Airway edema • Smooth muscle

vasodilation hyperplasia/hypertrophy

• Mucus • New vessel formation

hypersecretion
• Goblet cell hypertrophy

36
 Asthma:
Airway inflammation
(remodeling)

37
 Asthma: Clinical Features
• Dyspnea
o related to respiratory effort
o intermittent, often exertional
o exposures irritants (dust), allergens (ragweed),
physical (cold air), emotional factors

• Dry cough or yellow sputum

• Wheezing
o 30% of asthmatics
o nocturnal / post-exercise
o turbulent airflow due to airway narrowing
38
 Diagnosis of Asthma
Clinical history
• Episodic or persistent dyspnea, wheeze,
tightness, cough
• Triggers (allergic, irritant)
• Risk factors for asthma development

Objective evidence of reversible airflow obstruction

• Spirometry or PEFR
• Post-brochodilator spirometry
Ancillary Tests (Not always needed)
• Chest X-Ray
• Eosinophil count & IgE level
• Allergy testing
• Bronchoprovocation testing
39
 Objective evidence of
reversible airflow
obstruction in the patient
mentioned before

Forced Volume-Time curve Flow-Volume curve

40
 Differential Diagnosis:
COPD and Asthma

ASTHMA COPD
• Onset early in life (often • Onset in mid-life
childhood)
• Symptoms slowly
• Symptoms vary from day to day progressive
• Symptoms at night/early morning • Long smoking history
• Allergy, rhinitis, and/or eczema • Dyspnea during exercise
also present
• Largely irreversible airflow
• Family history of asthma limitation
• Largely reversible airflow
limitation
41
 ASTHMA COPD
Allergens Cigarette smoke

Epithelial cells Mast cell Alv macrophage Epithelial cells

CD4+ cell Eosinophil CD8+ cell Neutrophil

(Th2) (Tc1)

Bronchoconstriction Small airway narrowing

AHR Alveolar destruction

Airflow Limitation
Reversible Irreversible
42
 Pathophysiology Lecture 12
Topic: Restrictive Lung Diseases

Dr. S. Upadhya

1
Patient:
A 65-year-old man presents with gradually
progressive dyspnea and dry cough of 9-month
duration. There is no travel history or exposure to
toxins/dusts.

Physical Examination:
Tachypnea, Tachycardia, Digital clubbing.
Bibasilar inspiratory crackles & a loud P2
component of second heart sound on auscultation.

Investigations: Next slide

Diagnosis: Idiopathic Pulmonary

Fibrosis 2
Pulm Function Test Reports Imaging

3
 Restrictive Lung Diseases

Def: Diseases characterized by reduced total

lung capacity (TLC), either because of an
alteration in lung parenchyma or because of a
disease of the pleura, chest wall, or
neuromuscular apparatus.

4
Restrictive Lung Diseases: Classification

• PARENCHYMAL
• Acute: infection, inflammation, edema.
• Subacute/Chronic: Diffuse Interstitial Lung
Diseases (DILD)

• EXTRAPARENCHYMAL
• Kyphoscoliosis, Bilateral pleural diseases,
Massive obesity, Neuromuscular diseases &
Diaphragmatic paralysis.

5
 Pulmonary Function Tests:
Restrictive Lung Disease
Spirometry: Normal or increase in FEV1/FVC
Decrease in FVC, FEV1
Volumes: Decrease TLC (by definition)
RV: Decreased in parenchymal disease
Increased in neuromuscular disease
DLCO: Decreased in parenchymal disease
Normal in neuromuscular disease.

6
 Extra
parenchymal
Parenchymal

7
 Flow Volume Curve of Restriction
pattern (in Parenchymal diseases)
Normal
More vertically
oriented loop
+

Flow

1 2 3 4 Volume (Liters)
_
Patient: Blue curve
8
 Flow-volume curves: Parenchymal restrictive
VS Extraparenchymal restrictive disease

O: Obstructive disease

R(P): Parenchymal
restrictive disease
Flow

R(E): Extraparenchymal
restrictive disease with
limitation in inspiration
and expiration.

9
Restrictive Lung Diseases: Diffuse
Interstitial Lung Diseases (DILD)

10
 DILD: Etiology
Diseases of known etiology:
• Inorganic – pneumoconioses (Eg: asbestosis)
• Organic - hypersensitivity pneumonitis (Eg:
Farmer’s lung)
• Drugs – Eg: Nitrofurantoin, Cancer chemo &
Amiodarone.
• Other - radiation, lymphangitic carcinomatosis,
etc.

Diseases of unknown etiology:

• Idiopathic Pulmonary Fibrosis (IPF)
• Diseases with Collagen Vascular Disorders:
Dermatomyositis, Scleroderma, SLE.
• Sarcoidosis. 11
Diffuse Interstitial Lung Diseases (DILD):
Common features

Symptoms: Gradually progressive dyspnea with

exercise limitation +/- dry cough

Signs: Tachypnea with inspiratory crackles +/-

digital clubbing

Chest radiography: Reticular/nodular opacities;

Honeycombing in later stage.

12
 (General)

Diverse inflammatory
processes contribute to
excess fibroblast activity 13
 Idiopathic Pulmonary Fibrosis (IPF)
Presentation:
• Middle-aged or elderly patients
• Insidiously progressive dyspnea
• Dry cough
• Resting tachypnea & tachycardia
• Bibasilar inspiratory crackles (velcro crackles)
• Clubbing
• Evidence of pulm hypertension (loud P2)
• PFT: Restrictive pattern & diffusion defects
• Imaging: Diffuse infiltrates (reticular/nodular
opacities)

Other etiologies of DILD have to be ruled out!

14
 IPF: Pathology

❑The histologic hallmark is Usual Interstitial

Pneumonia (UIP).
❑Mostly affect the peripheral, subpleural lung
parenchyma.
❑Heterogeneous areas of normal lung,
interstitial inflammation, foci of proliferating
fibroblasts, dense collagen fibrosis, and
honeycomb changes.
❑Lymphoplasmacytic infiltrate in the alveolar
septa, associated with hyperplasia of type 2
pneumocytes.
❑The extent of fibroblastic proliferation is
predictive of disease progression. 15
 What is Usual Interstitial Pneumonia (UIP) ?
Morphologic combination of:
(1) Patchy interstitial fibrosis with alternating areas of
normal lung,
(2) Fibrosis characterized by scattered fibroblastic foci in
the background of dense acellular collagen, and
(3) Architectural alteration due to chronic scarring or
honeycomb change.

Normal Lung alveoli and UIP pattern seen in IPF

16
interstitium
 Honeycomb lung - End stage of IPF/UIP
Diffuse Interstitial fibrosis & cystic spaces

Autopsy lung
17
Peripheral subpleural fibrosis
more common in IPF

18
 IPF: When to biopsy

A clinical diagnosis of IPF can be made with

high degree of certainty in about 50-70% of
patients.
In patients with atypical symptoms or
radiological features, definitive diagnosis is
by surgical lung biopsy (Gold Standard).

19
 IPF: Complications

• Respiratory failure
• Pulmonary hypertension
• Cor pulmonale

20
Patient:
A 35-year-old African American woman presents with dry
cough of 5-month duration. She also has mild arthralgias and
painless skin nodules on her face, lips and extremities. There
is no history of chest pain or dyspnea.
Physical Exam:
Purplish non-tender skin papules. Unremarkable chest
findings.
Lab: ↓ RV; ↓ TLC and ↓ DLCO.
Normal FEV1/FVC.
Hypercalcemia.
Chest X-ray: Bilateral hilar lymphadenopathy with lung
infiltrates (Next slide)
Skin biopsy of nodule: Non-caseating granulomas.

Diagnosis: Sarcoidosis.
21
 Chest Radiograph: Sarcoidosis

Note: Bilateral hilar & mediastinal

lymphadenopathy with lower lung infiltrates 22
 Sarcoidosis: Pathogenesis
A multisystem disease of unknown etiology characterized by
non-caseating granulomas in many organs.

•Disease of disordered
immune regulation
•Antigen-presenting cell
and helper T cell
complex releases
multiple cytokines and
granuloma formation.
•Granuloma may
resolve or produce
chronic fibrosis.

23
 Sarcoidosis: Pathology

(25%)

(25%)
Parotid
(major,
75-90%)

(major,
90%) Non-caseating granuloma
with multinucleated giant
cells

24
Pulmonary Sarcoidosis: Granulomas in
lymphatic pattern in lung interstitium

Granulomas undergoing
fibrosis

25
 Sarcoidosis: Pulmonary Presentations

• Bilateral hilar lymphadenopathy + parenchymal

infiltrates

• Chronic upper lobe pulmonary fibrosis

• Lofgren’s Syndrome: Erythema nodosum

(tender, erythematous subcutaneous nodules) +
bilateral hilar lymphadenopathy + arthralgia.

26
Sarcoidosis: Extrapulmonary presentations

• Skin: Erythema nodosum, Lupus pernio

(voilaceous skin nodules on the face, lips, neck,
upper back and extremities).
• Eye: Uveitis, retinitis & dry eye.
• Hypercalcemia and hypercalciuria.
• Liver: Granulomatous hepatitis.
• Splenomegaly with granulomas.
• Joints: Peripheral pauci-articular arthritis.
• Cardiac: Arrhythmias, heart block.
• CNS: Meningitis, cranial n. palsy, brainstem
infiltrates, peripheral neuropathy.
• Renal: Interstitial nephritis, Glomerulonephritis,
Nephrocalcinosis & Urolithiasis.
27
Erythema
Lupus Pernio
Nodosum

•Grouped, nontender, firm

purple nodules or papules
•“Apple jelly” on diascopy
•Tender nodules mostly on •Non-caseating granuloma
the shin on histopathology
•Nonspecific inflammatory •Indicates severe, chronic
lesions disease involving multiple
•Hallmark of acute, benign organs.
and self-limited disease. 28
 Sarcoidosis: Lab findings

More common:
• Elevation of liver enzymes,
• Hypergammaglobulinemia &
• Elevated serum angiotensin-converting enzyme
(ACE)

Less common:
• Hypercalciuria & Hypercalcemia

Biopsy of hilar lymph node or skin nodule:

• Non-caseating granuloma.

29
Patient:
32-year-old woman presents with progressive dyspnea,
pleuritic chest pain and cough of 6 month duration. She also
noticed a rash on her face, alopecia and that her fingers will
change color when she is exposed to cold environments.
She denies occupational and environmental exposures.
She is not on any medications.
Physical exam:
A butterfly-shaped rash on the face;
Crackles on chest auscultation.
Lab:
CXR: diffuse infiltrates
Antinuclear antibodies: positive

Diagnosis: Diffuse Interstitial Lung

disease with SLE.
30
 DILD associated with Connective
Tissue Diseases
Rheumatoid Arthritis: Pulmonary Disease more
common in men with late onset rheumatoid.
Systemic Lupus Erythematosus: Acute lupus
pneumonitis and later DILD.
Scleroderma (Systemic Sclerosis): Strongly
associated with Raynaud’s phenomenon.
Ankylosing Spondylitis: Apical fibrobullous
disease is common.

31
 Pathophysiology Lecture 13

Topic: RESPIRATORY FAILURE

Dr. S. Upadhya

1
Patient:
A 67-yr-old woman with a 15-year history of type2 diabetes
presents to ER with fever, chills, back pain, dizziness,
dyspnea and a nonproductive cough of 4-day duration.
There is no history of chest pain.
Physical Examination:
Ill-appearing female. Vitals: Temp 39.6°C; HR 110; RR 38 &
BP 90/58 mmHg. She has marked right flank tenderness
and lung exam shows coarse rales and rhonchi throughout.
Lab:
ABG: 7.32; PaO2 64; PaCO2 66; HCO3 26 and an O2
saturation (SaO2) of 74%.
Urinalysis: Bacteriruria with many WBCs.
Blood culture is positive for E.coli.
Chest X-ray: Diffuse alveolar (air space filling) infiltrates.
Diagnosis: Acute Resp failure due to sepsis.
2
 Respiratory Failure (RF)

Definition: The loss of the ability to ventilate

adequately or to provide sufficient oxygen to
the blood or systemic organs.
Typically characterized as “hypoxemic” or
“hypercapnic”
Characteristics:
• PaO2 < 50-60 mmHg and/or PaCO2 > 45-50
mmHg
• PaO2/FiO2 ratio < 300
3
 Respiratory Failure: Terminology

Acute Respiratory Failure

• Derangement of respiratory function occurs
rapidly
• Emergent threat to the patient's life.

Chronic Respiratory Failure

• Abnormalities develop gradually
• Tolerated for weeks or longer, without
immediate threat to the patient's life.

4
 Respiratory Failure
Clinical Hallmarks

Symptoms
• Dyspnea, air hunger
• Agitation, confusion, disorientation, panic
• Coma

Signs
• Tachycardia, Hypertension,
• Diaphoresis, Cyanosis,
• Tachypnea & increased
work of breathing (WOB)

5
 Increased Work of Breathing

Work of Breathing: Energy spent for breathing. 6

 Causes of Respiratory Failure
Kyphosis,
Fibro & Pneumo COPD,
Brain thorax Asthma,
CHF Pneumonia,
Spinal Tumor,
PE ILD
Cord Vocal cord
Neuro- dysfunction
muscular
Thorax
CVA,
Pleura
medulla Upper
trauma
Airway Cardio/
Myastenia Gravis, pulm-
Guillian Barre Syndrome, vascular Lower
metabolic Airway/
Alveoli
7
 Respiratory Failure: Types

Hypoxemic Hypercapnic
• The Lung fails • Respiratory pump fails
(parenchymal diseases) (Extraparenchymal dis)
• Abnormally low PaO2 • Abnormally low PaO2
• PaCO2 typically low • Hypercapnia (PaCO2)
• Increased VA • Decreased VA
• More common • Less common
• Usually not associated • Associated with chronic
with chronic history. history such as COPD,
Neuro-muscular disorders.
8
 Arterial Hypoxemia
Definition: PaO2 is less than 80 mmHg.
Physiology:
PaO2 ∞ Ventilation (VA) and
1/ ∞ V/Q mismatch.
Causes of hypoxemia:
Decreased or inadequate FiO2
Decreased VA (Hypoventilation)
V/Q mismatch
A-a gradient
Intrapulm Shunt

(FiO2 = Fractional conc of O2 inhaled) 9

 A-a Gradient and Arterial Hypoxemia

• A-a gradient = Difference between alveolar and

arterial oxygen
A-a gradient = PAO2 – PaO2
Estimated from Estimated directly
*Alveolar gas from ABG
equation
Normal varies with age:
Age 20: 5-10; Age >80: 20-25.

Clinical usefulness of A-a gradient:

Along with the PaCO2 helps in differential diagnosis
of arterial hypoxemia.

(*Alveolar gas Equation: PAO2 = FiO2 (760 – PH2O) – PaCO2/0.8) 10

 Causes of Arterial Hypoxemia with or
without increased A-a gradient
A-a gradient
Low FiO2 Normal
Hypoventilation Normal
V/Q mismatch 
Intrapulmonary 
Shunt
V/Q mismatch examples: Pulmonary embolism,
Asthma, COPD.
Shunt examples: CHF & ARDS.
Hypoxemia with a Normal A-a gradient: Low PiO2
(High altitude)
Normal Pressures at Sea Level:

Oxygen pressure A-a Gradient =

at sea level= 100-95 =
150 mm Hg 5 (normal)
PAO2 = 100
PACO2 = 40

PvO2 = 40 mm Hg PaO2 = 95 mm Hg 12
Hypoxemia with a Normal A-a gradient: Low PiO2
(High altitude)
Air Pressure at Mount Everest peak (8848 m) is 250 mmHg
• Oxygen Pressure at this
altitude is also low.
• PAO2 is low.
• PaO2 is also low.

Therefore,
A-a gradient PAO2 = 44
remains within
PACO2 = 7.5
Normal range.

PaO2 = 37 mm Hg
13
 Hypoxemia with a Normal A-a gradient:
Hypoventilation (Low VA)
• A patient with overdose of a narcotic has a low
respiratory rate (Hypoventilation).
• His PaCO2 becomes high.
• His PAO2 becomes low (as per Alveolar gas
equation)
• His PaO2 is also low.

Therefore, A-a gradient remains within normal

range.

[Alveolar gas equation:

PAO2 = 0.21 (760-47) – PaCO2/0.8] 14
 Hypoxemia with Increased A-a gradient:
V/Q mismatch
• Areas of the lungs where ventilation and
perfusion are imbalanced.
• Normal ventilation-to-perfusion ratio (V/Q) is
4L/5L = 0.8.
• Imbalances can involve the alveoli, pulmonary
circulation or both.
• Examples of V/Q mismatch:
– Nonventilation/underventilation of perfused
alveoli (atelectasis, pneumonia, COPD)
– Nonperfusion of ventilated alveoli (pulmonary
embolus)
– Underperfusion of ventilated alveoli
(hypotension, hypovolemia and shock) 15
 Hypoxemia with Increased A-a gradient:
Intrapulmonary Shunts
• Blood circulates past congested alveoli
without becoming oxygenated (oxygen is
unable to diffuse across the alveolar-capillary
membrane).
• Blood returns to the left side of the heart
unoxygenated.
• Examples: ARDS, massive pneumonias,
pulmonary edema (acute LVF).
• Shunts immediately lower PaO2, but PaCO2
does not rise until the shunt reaches ~ 50%
• Inhaling high concentrations of oxygen does
not reverse hypoxemia
16
 Arterial Hypoxemia: Response to
increasing inspired air O2

A-a PaO2
gradient
Low FiO2 N Improves

Hypoventilation N Improves

V/Q mismatch  Improves

Intrapulmonary  No change
Shunt
Example of Hypoxemia in an obstructive
pulmonary disease: Acute Asthma

• No parenchymal
disease

• VA/Q mismatch due to

airway disease

• Test: Spirometry shows

obstruction

18
Example of Hypoxemia in
Thromboembolic disease

• No parenchymal
disease

• VA/Q mismatch due

to Pulmonary
vascular disease

• Test: Lung scan &

Spiral CT

19
Example of Hypoxemia in the Presence of
massive Parenchymal Disease: Lobar
pneumonia

▪Extensive
airspace disease

▪Intrapulmonary
shunt

▪Severe
Hypoxemia

20
 Hypoxemia with Hypercapnia
(Failure of the ‘Ventilatory Pump’)

21
 Hypoxemia with Hypercapnia
PaCO2 ∞ CO2 production and
1/ ∞ ventilation

Alveolar Ventilation Equation:

PaCO2 ∞ VCO2
VA
PaCO2 ∞ VCO2
VE (1-VD/VT) 22
 Alveolar Ventilation Equation

PaCO2 = K VCO2
VE (1-VD/VT)
• VCO2 = Carbon Dioxide production
– VE = Minute ventilation
– VD = Dead space ventilation
– VT = Tidal volume

23
 Causes of Hypercapnia
Increased CO2 production (metabolic rate):
•Increased activity
•Sepsis
•Thyrotoxicosis

Decreased Alveolar Ventilation:

•Decreased minute ventilation
•VD/VT increases, with constant minute
ventilation: As in Rapid, shallow breathing
& V/Q mismatch.

24
Respiratory Failure due to Ventilatory
Pump failure: Possible sites

25
 Examples of Hypoventilation

• Disorders of the Spinal Cord

• Cervical cord injury (C3)
• Tetanus

• Anterior Horn Cell Disorders

• Amyotrophic lateral sclerosis
• Poliomyelitis
• Rabies

26
 Examples of Hypoventilation (contd)

•Disorders of Peripheral Nerves:

• Guillain-Barré syndrome
• Diphtheria
• Porphyria
• Tick paralysis
• Fish toxins

27
 Examples of Hypoventilation (contd)
• Disorders of Neuromuscular junction:
– Myasthenia gravis
– Eaton-Lambert syndrome
– Organophosphate poisoning
– Botulism
• Disorders of Respiratory center:
– Narcotic overdose
– Meningitis/encephalitis
– Raised intracranial pressure

28
Features of respiratory failure due to pump failure
Hypo Hyper
ventilation ventilation
• Occurs in diseases

Alveolar Partial Pressure (mm Hg)

involving the
extrapulmonary
compartment
• Impaired or low
alveolar ventilation
• Hypercapnia
(↑PaCO2)
• Respiratory acidosis

Normal ventilation

29
Alveolar ventilation
 ABG helps to differentiate Hypoxemia
with Acute Vs Chronic Respiratory
acidosis
Patient A Patient B
(Chronic) (Acute)
PO2 66 66

PCO2 91 91

HCO3 49 30

pH 7.36 7.25

•PaCO2 is elevated and PaO2 is low in both.

•Acute respiratory acidosis is accompanied with acidemia
(ie, pH < 7.35).
•In chronic respiratory acidosis, the pH is normal or near-
normal secondary to renal compensation with an elevated
serum bicarbonate (ie, >30 mEq/L).
Examples of Respiratory Failure of
Hypoxemic but Normocapnic type

• Acute Resp Distress Syndrome

(ARDS) aka Acute Lung Injury
(ALI)

31
Acute Resp Distress Syndrome (ARDS)
aka Acute Lung Injury (ALI)
Clinical syndrome of severe dyspnea of rapid
onset, hypoxemia, and diffuse pulmonary
infiltrates leading to respiratory failure.

3 clinical features:
• Widespread, bilateral radiographic
infiltrates
• PaO2/FiO2 ratio of less than or equal to
300 mmHg, regardless of the level of
oxygenation
• No clinical evidence for an elevated left
atrial pressure.
32
Acute Lung Injury (ALI)

• Acute clinical syndrome

• Occurs within 1 week of
an initial insult
• Bilateral pulmonary
infiltrates
• Hypoxemia (PaO2/FiO2
<300)
• Pulm edema NOT
explained by left atrial
hypertension

33
ARDS: Causes and Predisposing Conditions

Direct lung injury Indirect lung injury

• Pneumonia • Sepsis
• Aspiration of • Severe trauma with
gastric contents shock and burns
• Pulmonary • Cardiopulmonary
contusion bypass
• Fat emboli • Drug overdose
• Near-drowning • Acute pancreatitis
• Inhalational injury • Massive transfusion
• Reperfusion injury of blood products

34
ARDS: Pathophysiology

•↑ pulm capillary
permeability by injury
•↑ alveolar epithelial
permeability by injury
•Protein-rich fluid in the
interstitium & alveoli
•“Non-Cardiogenic
pulmonary edema”
•Normal pulm hydrostatic
pressure.

35
 Cardiogenic Vs
Non-cardiogenic
edema

Hydrostatic Pr in pulm cap

is increased in cardiogenic
pulmonary edema but
NOT in non-cardiogenic
edema

36
37
 Classification of Hypoxia based on
Oxygen transport (DO2)
Oxygen delivered to tissues (DO2) depends on:
Hb-bound Oxygen, PaO2 and Cardiac Output

Hypoxemic hypoxia
DO2 is reduced because of a Low PaO2

Anemic hypoxia
DO2 is reduced because of a Low functional
Hb concentration
38
 Classification of Hypoxia based on
Oxygen transport (DO2)-contd

Circulatory hypoxia
DO2 is reduced because of a Low Cardiac output

Histotoxic hypoxia
DO2 normal, but cellular metabolic pathways are
blocked (e.g., cyanide poisoning)

39
Directed Learning Activity (DLA)
in Pulmonology

Topic:
PNEUMONIAS & TUBERCULOSIS

1
This DLA must be studied
before attending IMCQs in
Pulmonology

2
Normal Defenses Against Pulmonary
Infections

• Gag and Cough reflex

• Mucociliary escalator
• Cellular defenses
– Macrophages
– Neutrophils
– Lymphocytes
• Extracellular soluble mediators

3
 Cough
Definition: A forceful expulsion of air from the lungs
which is initiated by the irritation of cough receptors
that exist in the epithelium of the upper and lower
respiratory tracts.
Acute: < 3 weeks
Subacute: 3-8 weeks
Chronic: > 8 weeks

Differential diagnosis of cough:

• Asthma • Tuberculosis
• Post-nasal drip • COPD
• Gastroesophageal Reflux • Foreign Object
• Bronchitis/Pneumonia • Ca lung
4
 Key Definition: Pneumonia

• Pneumonia is inflammation of the lung,

resulting in consolidation due to exudate
within lung tissues and airspaces.
• Note: although ‘pneumonitis’ is technically a
synonym for pneumonia, this term is
clinically applied when referring to an
interstitial type of pneumonia.

5
 Pathogenesis of Pulmonary Infections

Step 1: Entry of the pathogen

– Aspiration (ie., Anaerobic oral flora mixed with
aerobic bacteria)
– Inhalation (ie., Mycobacteria & viral pathogens)
– Inoculation (contaminated equipment)
– Colonization (in patients with COPD)
– Hematogenous spread (patients with sepsis)
– Direct spread (adjacent abscess)

6
 Pathogenesis of Pulmonary Infections

Step 2: Replication & Spread of the pathogens

because of virulence factors of the pathogens
and reduced host immunity.
Examples:
-Pneumolysin from Strept. Pneumoniae is
cytotoxic to respiratory epithelium & directly
inhibits immune and inflammatory cells and
activates complement.
-Pili of Pseudom. aeruginosa play important role
in the attachment to host cells.

7
Pathogenesis of Pulmonary Infections

Step 3: Establishing Tissue Damage in two ways:

• Direct damage (ie viral cytopathic effects)
• Activation of host defense systems by:
– Acute inflammatory response (bacterial
pathogens)
– Cellular immune response (fungal &
mycobacterial pathogens)

8
 Pathophysiology of Pneumonia
Host inflammatory response occurs when the microbial
load/virulence exceeds the capacity of alveolar
macrophages to kill microorganisms
↓
Release of inflammatory mediators (IL-8 and granulocyte
colony-stimulating factor) from alveolar macrophages that
recruits blood neutrophils to the lung
↓
Inflammatory mediators released by macrophages and the
newly recruited neutrophils create an alveolar capillary leak
↓
a. Hypoxemia due to O2 diffusion defect
b. Decreased pulm compliance Produces
c. Bronchoconstriction (in some) dyspnea
d. Rales on auscultation
e. Radiographic infiltrate 9
 Pathophysiology of respiratory failure
in Pneumonia

Changes in diffusion Changes in lung mechanics:

and Hypoxemia: • Reductions in lung
• Increased volume
respiratory drive • Reduction in compliance
• Respiratory • Intrapulmonary shunting
alkalosis of blood

Respiratory failure
10
Clicker Time

11
A 65-yr-old woman presents with a 4-day history of
fever, productive cough and dyspnea. His sputum
culture is positive for encapsulated gram positive
cocci that are in pairs. His chest X-ray shows lobar
pneumonia on the left lower lobe. The patient’s
dyspnea is primarily due to which of the following?
20% 20% 20% 20% 20%
A. Inadequate perfusion
B. Increased ventilation
C. Increased airway resistance
D. Increased lung compliance
E. Poor oxygen diffusion A. B. C. D. E.
12
Types of Pneumonia: Based on how a person
gets infection

• Community-Acquired pneumonia (CAP)

• Hospital-Acquired pneumonia (HAP &
also known as Nosocomial pneumonia)
• Aspiration pneumonia (AP)
• Pneumonia in immunocompromised host
(PIH)

13
Types of Pneumonia: Based on Anatomic or
radiologic distribution of lung infection

•Lobar pneumonia (also known as

Focal or Nonsegmental pneumonia):
Confluent in distribution

•Multifocal/lobular pneumonia
(Bronchopneumonia): Patchy
distribution

•Interstitial pneumonia (Focal diffuse)

14
Patient:
A 32-year-old otherwise healthy, man presents
with a 3-day history of cough, fever, purulent
sputum and dyspnea. There is no history of
travel.
Physical exam:
Temp: 38.5oC, Resp Rate: 32/min, BP:130/75
mmHg & HR 110/min.
Chest examination: Dullness to percussion &
Increased vocal fremitus, Bronchial breath
sounds and crackles over right middle lobe
on auscultation.
15
 Chest X-ray of Patient 1 Normal Chest X-ray

Diagnosis: Community acquired Lobar Pneumonia

16
Community Acquired Pneumonia (CAP): Major
pathogens
Typical “Atypical’
Pulmonary Symptoms Prominent extrapulmonary symptoms
are predominate like GI/Nervous/joint symptoms

Abrupt onset Insidious onset

Purulent sputum Dry cough, mucoid sputum

Consolidation on CXR Diffuse pulmonary infiltrates

Major pathogens: Major pathogens:

• Strep. pneumonia • Mycoplasma pneumonia
• H. Influenza • Chlamydia
• Staph. Aureus • Legionella
• Klebsiella • Viruses (Influenza, RSV & Adeno)
Lobar (Focal or Nonsegmental) Pneumonia

•Nonsegmental,
homogeneous
consolidation
involving one lobe.
•Pleuritis is
common.

18
Bronchopneumonia (Multifocal or lobular
pneumonia)

•Involves bronchi,
bronchioles & alveoli
•Patchy distribution
•More than one lobe
•Pleuritis is less
common.

19
 CAP: Radiology

Lobar Bronchopneumonia
20
 Atypical pneumonia: Legionella
Diversity of presentations: Pathogen:
• Cough L. Pneumophilia is the
• Fever most common
• Headaches Aerobic, waterborne,
• Myalgias gram-negative,
• Hyponatremia unencapsulated,
• Obtundation nonmotile, catalase-
• Hemoptysis positive, and weakly
• Nausea, diarrhea oxidase +ve bacillus.
Diagnosis: Gram stain - no organisms
• Sputum direct fluorescent antibody (2-4 hours)
• Culture on charcoal yeast extract (3-5 days)
• Legionella urinary antigen (1-3 days)
• Serology for antibody titer (>3 wks into course)21
 Hospital-acquired (or Nosocomial)
Pneumonia
• Occurs after 72 hours of hospitalization (mostly
in intensive care units).
• Primary route of entry is microaspiration of
oropharyngeal contents into trachea.
• Less common routes include inhalation & blood
• Pathogenesis: Altered host immunity, increased
oropharyngeal flora & translocation of gastric
bacteria to airways by nasogastric tube.
• Major pathogens: P. aeruginosa, Kl. pneumoniae,
E. Coli & Serratia marcescens (Gram -ve rods);
Staph. aureus (mainly Methicillin-resistant Staph
aureus) and Acinetobacter. 22
 Aspiration Pneumonia: Features
• Aspiration of oropharyngeal or gastric contents.
• A predisposing condition for aspiration exists –
Altered consciousness (alcohol intoxication, drug
overdose & neurological disease) or esophageal
diseases.
• Impaired airway defense mechanisms increase
virulence of the infectious agents.
• Major pathogens: Aerobic Gram +/- bacteria
(Pneumococci, Staph. auerus, H. influenzae,
pseudomonas and enterobacteria) and also Oral
anaerobes.
• Putrid expectoration (if due to anaerobic infection).
• Radiology shows evidence of pulmonary necrosis.23
 Anaerobic Pathogens: Features
•From aspiration of oropharyngeal contents.
•Major pathogens: Peptostreptococcus,
Bacteroides, Fusobacterium, Prevotella and
microaerophilic streptococci.
•Frequently found in aspiration pneumonia,
empyema, lung abscesses
•Characterized by foul smelling (putrid) and bad
tasting sputum.
•Produce cavitation or numerous small abscesses
that spread to involve several pulmonary segments
(necrotizing pneumonia).

24
 Radiographic Features of Anaerobic
bacterial (necrotizing) pneumonia
•An infiltrate with or without
cavitation in dependent
segments of the lungs (ie,
posterior segments of upper
lobes, superior segments of
lower lobes in supine).
•Lucency within the infiltrate
(necrotizing pneumonia).
•Air-fluid levels within a
circumscribed infiltrate (lung
abscess)
•May have an evidence of
parapneumonic pleural effusion Right-lower-lobe lung
abscess in a 60-year-old
(Not seen in this X-ray). alcoholic patient
25
Patient:
34-yr-old man presents with a 5-day
history of cough, fever, purulent
sputum and dyspnea. He was found
to be HIV positive 3 years ago.
Vital signs: T 39oC, RR 34, BP 115/70
HR 110
Chest Auscultation: diffuse crackles all
over.
ABG: PaO2 44, PaCO2 32, pH 7.47,
HCO3 23.
X-ray: Diffuse bilateral infiltrates
Lab: Smear from bronchoalveolar lavage
shows cysts of Pneumocyctis jirovecii
(arrows in smear on the right).
26
Pneumonia in immunocompromised host
(PIH): Features
• Bacterial pathogens: Myco Tuberculosis and avium.
• Fungi: Pneumocystis jirovecii, Aspergillus fumigatus,
Histoplasma capsulatum, Coccidioides immitis and
Cryptococcus neoformans.
• Viruses: Cytomegalovirus, influenza, herpes simplex
virus, varicella zoster virus.
• Superinfection by bacterial pathogens that cause
community-acquired pneumonia.
• Gets complicated with empyema, sepsis,
pneumothorax, and acute respiratory distress
syndrome (ARDS).
• Often needs invasive diagnostic testing-
Bronchoalveolar lavage and lung biopsy studies.
27
Complications of Pneumonia

Acute:
• Parapneumonic effusion
• Lung abscess
• Empyema
• Respiratory failure

Chronic:
• Bronchiectasis

28
Complication of Pneumonia: Lung abscess
•Def: Necrosis of pulm tissue and formation of
cavity containing necrotic debris by infection.
•Multiple small (<2 cm) abscesses indicates
necrotizing pneumonia.
•Most common pathogens: Streptococci,
Anaerobes, Klebsiella, Pseudomonas and Staph
aureus.
•May take 1-2 wks in case of anaerobes and
early in others.
•PE: Amphoric or cavernous breath sounds with
or without concomitant consolidation findings
and finger clubbing.
•Chest X-ray shows cavity with a air-fluid level. 29
Complication of Pneumonia: Empyema
Def: Pus in pleural space.
Pathophysiology: Parapneumonic effusion gets
infected and neutrophils buildup.
Risk factors: Patients who have pneumonia due
to immunosuppression, aspiration, poor dental
hygiene and chronic lung disease.
PE: Egophony, Tubular breath sounds, Reduced
breath sounds and Dullness to percussion.
Chest X-ray: A) Extension of the air-fluid level to
the chest wall (extension of the air-fluid level
across fissure lines;
B) Tapering border of the air-fluid
collection (loculated empyema). 30
 Empyema: Chest X-ray

A B
A. Right-sided empyema showing extension of the
air-fluid level to the chest wall;
B. Left-sided loculated empyema showing pleural-
based opacity (arrow) with tapering obtuse margins.
31
CHRONIC BACTERIAL PNEUMONIA:
PULMONARY TUBERCULOSIS

32
 Patient 3:
26-year-old female engineering student from
China presents with cough, purulent sputum
production for 3-4 month, intermittent
streaking of blood in sputum.
She is a non smoker, no
immunosuppression. She lost 10kg wt loss
during this period.
Physical exam:
Vitals: T 38oC, RR 26, BP 130/75 HR 90
Auscultation: nil
Chest X-ray: Patchy consolidation in the left
upper lobe (Next slide).
33
Chest X-ray of the patient (arrow)

Diagnosis: Reactivation TB 34
Natural History of TB

35
 Definitions
• Latent TB infection (LTBI): A condition in
which an individual has inhaled particles
containing M. tuberculosis but does not
exhibit signs/symptoms of active TB.
• Reactivation TB (aka Secondary TB): Active
infection with symptoms and signs in a
previously sensitized host; highly contagious.
• Primary TB: Infection of an individual lacking
a previous contact with the tubercle bacilli.
– Primary pulmonary focus = Ghon focus
– Primary focus + regional lymph node
involvement = Ghon complex
36
 Tuberculosis - Worldwide

• 4th leading cause of death worldwide

• Kills more people than all other infectious
diseases combined
• Areas of highest prevalence:
– Southeast Asia (Pakistan, Bangladesh,
India, Indonesia, Myanmar and Thailand)
– Western Pacific (China, Japan)
– Africa

37
 Tuberculosis: Microbiology
Cell structure of Mycobacterium
tuberculosis:
– Basic bacterial cellular structure
– Unique waxy cell wall:
• Cannot gram stain
• Must use special Acid fast stains
– Major virulence factors:
• Waxy cell wall - lipid rich mycolic acids
stimulate cell-mediated immune response
reaction
• Cord factor (trehalose 6, 6' dimycolate) -
inhibits phagosome-lysosome fusion

38
Delayed
hypersensitivity &
Caseous granuloma
formation

39
Pulmonary lesions in TB:
Macro: Caseous necrosis and cavitation
Micro: Caseous granuloma with fibrosis & calcification.

40
 Diagnosis of Tuberculosis

• Medical history
• Physical examination
• Mantoux tuberculin skin test
• Chest radiograph
• Bacteriologic exam (smear and culture)
• Interferon-Gamma Release Assay (IGRA)
• Nucleic acid amplification test for the
mycobacterium

41
 Chest Radiograph

• Abnormalities often found in apical or posterior

segments of upper lobe or in superior segments of
lower lobe
• Cannot confirm diagnosis of TB; May be used to
support pulmonary TB in a person who has a
positive skin test but no symptoms of the disease. 42
 Diagnosis of TB: Interferon-Gamma
Release Assay (IGRA)

• Tuberculin skin tests may not be ideal since

there can be some difficulty evaluating the
skin test in patients who have received BCG
vaccination and in those with prior infection
with nontuberculous mycobacteria.
• IGRA is more specific in the diagnosis of LTBI
by Mycobacterium tuberculosis.
• IGRA measures T-cell interferon-gamma
response to antigens that are highly specific
for M tuberculosis and absent from the BCG
vaccine and M avium.

43
Screening for TB: Mantoux Skin Test

❑ Identifies infected persons at high

risk for disease (LTBI individuals) who
would benefit from preventive therapy,
❑ Identifies persons with active TB
disease who need treatment

44
 Groups to Screen with the (Mantoux)
Tuberculin Skin Test
• Persons with or at risk for HIV infection
• Close contacts of persons with infectious TB
• Persons with certain medical conditions
• Persons who inject drugs
• Foreign born persons from TB endemic
areas
• Medically underserved, high-risk
populations
• Residents of long-terms facilities
• Persons with occupational exposure such
as silicosis

45
 Administering Tuberculin Skin Test

• Inject intradermally 0.1 mL

of 5 TU PPD tuberculin

• Read reaction 48-72 hours

after injection

• Measure induration & record

reaction in millimeters

• If positive without symptoms

means LTBI.

46
CDC Guidelines: Classifying Tuberculin Reaction:
Cutoff of 15 mm or more induration is TB positive
in
• All persons with no known risk factors for TB.

Reactions in patients who have received BCG

vaccine should be interpreted in the same way as
the reactions above, regardless of BCG history,
according to guidelines from the CDC.

47
CDC Guidelines: Classifying Tuberculin Reaction:
Cutoff of 10-14 mm induration is TB positive in

• Recent immigrants (within the last 5 yrs) from

high-prevalence countries.
• Persons who inject drugs (if HIV negative).
• Persons with the following conditions that place
them at high-risk: Silicosis, Diabetes, Renal
failure, Certain malignancies & Leukemias.
• Medically underserved & prisoners.
• Residents of long-term care facilities.
• Children & adolescents exposed to adults at
high-risk.

48
CDC Guidelines: Classifying Tuberculin Reaction:
Cutoff of 5-9 mm induration is TB positive in

• Persons known to have or suspected of having

HIV infection
• Close contacts of a person with infectious TB
• Persons who have a chest radiograph suggestive
of previous TB
• Persons who inject drugs (if HIV status unknown)
• Patients with organ transplants and other
immunosuppressed patients receiving the
equivalent of >15 mg/day of prednisone for one
month or more.

49
Clicker Time

50
A 29-yr-old man from Grenada, recent immigrant
to US, presents to local health dept for a recent
PPD of 12 mm of induration. There is no signs or
symptoms of TB. He received BCG as a child. His
chest X-ray is normal. What is most appropriate
interpretation of the PPD and suitable
management for this patient?
A. PPD positive and no TB therapy indicated 25%
25%
B. PPD positive and INH prophylaxis indicated
C. PPD considered a false positive given his 25%
prior BCG administration
25%
D. PPD considered negative and no treatment
indicated
51
Directed Learning Activity
(DLA) in Pulmonology
Topic: Pulmonary Vascular
Diseases

1
This DLA must be studied
before attending IMCQs in
Pulmonology

2
Patient:

A 38-year-old homemaker complains of a 6-month

history of dyspnea both at rest and during exercise, and
swelling in her legs and feet. Initially she had vague
symptom of easy fatigue.

Physical examination:
Distended jugular veins, hepatomegaly, ascites and
pitting edema in her legs.
Cardiac auscultation: Loud P2 component of second
sound; An audible fourth heart sound over tricuspid area.

Diagnosis: Right heart failure due to pulmonary

arterial hypertension (PAH).

3
Characteristic X-ray of a patient with PAH

Prominent central (main)

Pulmonary artery

Prominent right cardiac

border (Enlarged RV)

“Peripheral arterial
pruning & oligemia of
the lung fields”

4
 Comparison between Pulm circulation and
Systemic circulation

Low Resistance, High Resistance,

Low pressure High pressure
circuit circuit

PVR = PPA – PLA

SVR = PA – PRA
Q
Q
= 100 – 0 = 20
= 15 mmHg – 5 mm Hg = 2 mmHg/L/min
5
5 L/min mmHg/L/min
5
Normal Distribution of Pulmonary
blood flow
PA =Alveolar air Pr
Pa=Pulm arterial Pr
Least Pv=Pulm venous Pr

6
 Classification of Pulm Hypertension

• Idiopathic pulmonary arterial hypertension:

Without identifiable cause

• Secondary pulmonary arterial hypertension:

An increase in pulmonary artery pressure
due to:
• Intrinsic parenchymal lung disease,
• Disease extrinsic to the lung

7
 Pulm Vascular Resistance (PVR)

Pulm Artery Pr – Left Atrial Pr (LAP)

PVR =
Cardiac Output (CO)

Pulm Artery Pr = (CO x PVR) + LAP

Note: (Ppv = LAP = PWP)

8
 Pathophysiology of Pulm Hypertension

Pulm Artery Pr = (CO x PVR) + LAP

• Increased volume of pulmonary flow (CO)

• Increased resistance in the pulmonary
vascular bed (PVR)
• Increased pulmonary venous pressure
(Ppv/LAP)

Note: (Ppv = LAP = PWP)

9
 Pulm Hypertension: Increased CO
Conditions: Congenital heart disease associated with
left-to-right shunt (VSD, ASD & PDA).
Left-to-right shunting of blood
↓
Increased pulm blood flow
↓
Endothelial injury due to increased shear forces
↓
Irreversible pulm vascular injury
↓
Increased pulm vascular resistance (PVR)
↓
Right-to-left shunting of blood (Eisenmenger Syndrome)
 Pulm Hypertension: a) Increased PVR
Conditions: COPD, Hypoventilation syndromes, high altitude.
Mechanism: Hypoxic vasoconstriction.
 Pulm Hypertension: b) Increased PVR
Conditions: Difffuse interstitial lung diseases,
Vasculopathies, Thromboembolic diseases.
Mechanism: Decreased pulm vascular area & fibrosis.
Endothelial cell
dysfunction
↓
Decreased production of
nitric oxide &
prostacyclin and
increased endothelin
↓
Vasoconstriction and
thrombogenesis
 Chronic Respiratory Disease

Acidosis &
Reduced Vascular Hypoxia Hypercapnia
Bed

Polycythemia &
Hyperviscosity Pulmonary
Hypertension

Cor Pulmonale
RVF
13
 Pulm Hypertension: Increased LAP
Conditions: Mitral stenosis, Pulm venous hypertension.
RV hypertrophy on ECG

15
In primary pulmonary
hypertension, the pulm function
test report will be:

Normal FVC,
Normal FEV1
Normal FRC & RV, but
Decreased DLco.

16
Patient:
A 34-year-old obese woman is recovering from an
uncomplicated cholecystectomy. On the fifth postoperative
day, she develops sudden onset of severe shortness of
breath. Her past medical history is significant for arterial
hypertension.
Physical Examination:
Vitals: Temp 38.5oC, BP 116/74, RR 28, HR 110.
She is diaphoretic.
Cardiovascular, respiratory system exam is unremarkable.
Lab:
Blood gases: PaO2 60mmHg, PaCO2 32mmHg, pH 7.47 &
HCO3 24 mEq/L.

Diagnosis: Acute Pulmonary Embolism.

17
Acute Pulm Embolism: Pathophysiology
Hemodynamic consequences:
Immediate loss of cross-sectional
area of the pulmonary vascular
bed
↓
Acute increased PVR and RV
afterload
↓
Elevated jugular venous
distention and peripheral edema.
Pulmonary Embolism: Predisposing
factors
▪ Age
▪ Recent surgery
▪ Immobility
▪ Co-existing (or previous) phlebitis
▪ Hormonal status (oral
contraceptives, pregnancy)
▪ Malignancy

19
 Acute Pulmonary Embolism: Clinical
Features

Symptoms Signs

• Dyspnea • Tachypnea
• Chest pain-pleuritic • Tachycardia
• Cough • Obvious DVT
• Hemoptysis • Cyanosis
• Wheezing • Pleural friction rub
• Palpitations • Hypotension
• Light headedness • Fever

20
 Diagnostic Tests:
Which one to choose?

• Chest X-ray
• Arterial Blood Gases
• Electrocardiogram (EKG)
• D-Dimer
• Venography, Doppler ultrasound
• Ventilation-Perfusion Lung scans
(V/Q)
• Spiral CT pulm angiography-Highly
sensitive

21
 Pulmonary Embolism: Chest X-ray Findings
First most common: Elevation of ipsilateral hemidiaphragm.
Second common finding: Atelectasis.

Embolism Without pulm Embolism with pulm infarction

infarction (90% cases): (10% cases):
• Focal decreased • Wedge-shaped consolidation
pulmonary vasculature (50%)
distal to embolus • Truncated cone shape
(“Westermark sign”). consolidation with the base
against the pleural surface
(“Hampton hump”).

22
 Pulmonary Embolism: Other Investigations

Blood Gases:
• May be normal!
• Hypoxemia may be present (not always)
• Increased A-a gradient (correlates with severity)
• Respiratory alkalosis (if hyperventilating).

EKG:
• Tachycardia, S1Q3T3 pattern (Tall S wave in lead I,
tall Q and inverted T in lead III).

These findings are nonspecific and neither necessary

nor sufficient to make the diagnosis.
23
 A-a gradient

• A-a gradient = Difference between alveolar and

arterial oxygen pressures.
A-a gradient = PAO2 – PaO2
Estimated from Estimated directly
*Alveolar gas from ABG
equation

Normal varies with age:

Age 20: 5-15; Age >80: 25-35.

Increased A-a gradient in: V/Q mismatch & Shunt.

(*Alveolar gas Equation: PAO2 = FiO2 (760 – PH2O) – PaCO2/0.8)

24
Lung Scans and Pulmonary Emboli

Arrow indicates low perfusion area due to

embolus in the right apex.

Perfusion (Q) Ventilation (V)

This creates V/Q mismatch and hypoxemia.

25
Spiral CT of thorax showing thrombus

Aorta
Pulmonary
Artery

Thromboembolus

Thromboembolus

26
Clicker Time

27
A 47-yr-old woman who had a surgery to her left
knee and was immobile, developed pain in left
lower extremity and swelling. 2 days later, she
developed sudden dyspnea and chest pain. She
was hyperventilating. Physical examination of RS
and CVS was unremarkable. Increase in which of
the following is most likely in her?

20% 20% 20% 20% 20%

A. PaO2
B. PaCO2
C. Left atrial pressure
D. A-a gradient
E. Airway resistance
A. B. C. D. 28 E.
Directed Learning Activity (DLA):
Pulmonology

Topic: Lung Cancers

1
Patient presentation:
A 64-year-old woman with a 15-year history of
chronic bronchitis presents with unproductive
cough and hemoptysis of 2-day duration. She has
20 lbs wt loss in the last 4 weeks. There is no
history of chest pain or bone pain.
Physical Examination: Unremarkable.
Chest X ray: shows consolidation in right lung
Bronchospy: Growth in the right bronchus.

2
 Lung Cancer: Etiology

• Smoking
• Radiation Exposure
• Environmental/ Occupational Exposure
– Asbestos
– Radon
– Passive smoke

3
 Classification

• Small cell (SCLC): ~20%

• Non small cell (NSCLC): ~75%. Includes

adenocarcinoma, squamous cell carcinoma &
large cell carcinoma.

• Others: ~5% & rare.

4
 WHO Histologic Classification
• Squamous cell carcinoma (30%)
• Adenocarcinoma (31%)
• Small cell carcinoma (20%)
• Large cell carcinoma (10%)
• Combined carcinoma (2%)
– Adenosquamous ca
– Small cell + adenocarcinoma
• Carcinoid Tumor (4%)
• Metastatic carcinoma (3%)

5
 Clinical Presentation
• Symptoms related to the primary lesion

• Symptoms related to intrathoracic spread

• Symptoms related to distant metastasis: Most

common with small cell ca

• Paraneoplastic syndromes

6
Symptoms & signs related to the primary
lesion in the lung

Central Tumors Peripheral Tumors

•Cough •Pain
•Hemoptysis •Dysnea
•Dypsnea •Pleural effusion
•Wheezing •Cough
•Postobstructive
pneumonia

7
 Intrathoracic Metastasis: Clinical
presentations

• Superior vena cava obstruction (SVC syndrome)

• Hoarseness (Recurrent laryngeal nerve)
• Elevated hemidiaphragm, dyspnea or hiccups
(Phrenic n)
• Horner syndrome (Brachial nerve root comp)
• Dysphagia (Esophageal compression)
• Worsening dyspnea (Airway compression)
• Pancoast tumor syndrome

8
 Intrathoracic Metastasis: Clinical
presentations

• Pericardial involvement causes pericardial

effusions, tamponade, or dysarrhythmias
• Pleural involvement causes dyspnea, cough
and chest pain
• Chest wall, ribs, or vertebral bodies -
localized pain, pleural effusions, or paresis.

9
Superior vena cava syndrome

•Edema of head, neck or arms

•Cyanosis
•Facial plethora
•Distended superficial veins
•Cerebral edema
•Airway compromise
•Hemodynamic compromise

10
 Horner’s Syndrome

Ptosis: Drooping of the eyelid

Miosis: Constriction of the pupil
Anhidrosis: Decrease in
sweating
Enophthalmos: Sinking of the
eyeballs into the face or the
orbital area.

Cause: Brachial nerve root

compression by tumor at T1
damaging preganglionic
cervical sympathetic fibers or
inferior cervical ganglion. 11
 Pancoast tumor syndrome

•Lung cancer arising from apical region

with destructive lesions of the thoracic inlet
and involvement of the brachial plexus and
cervical sympathetic nerves.
•Pain in the shoulder region radiating along
the ulnar aspect of the hand
•Atrophy of hand and arm muscles
•Horner syndrome
•Compression of the blood vessels with
edema
•Etiology: NSCLC located in the superior
sulcus. (Refer to the next slide for anatomy of
superior sulcus) 12
 Pancoast tumor

Vagus nerve
Sympathetic trunk
Brachial plexus
Recurrent Laryngeal nerve
Subclavian artery & vein

MRI thorax

13
 Superior sulcus of Rt. lung
Anterior Posterior
Rt. Subclavian artery
1st Rib
Rt. Subclavian vein

Rt. Brachiocephalic vein

Lt. Brachiocephalic vein
Superior vena cava
Bronchus to superior lobe
Pulmonary artery Bronchus to mid & low lobes
Pulmonary veins Esophagus
Cardiac region Azygos vein

Inferior vena cava

Diaphragm region
Superior sulcus refers to a pleuro-pulmonary groove formed by subclavian artery as
it curves in front of the pleura runs upward and lateral immediately below the apex.
14
It is a typical location for Pancoast tumor.
 Paraneoplastic syndromes
Clinical features Commonly associated
histological type
Hypercalcemia Squamous cell ca (PTHrP secretion)
Trousseau syndrome Adenocarcinoma (Hypercoagulability)
Clubbing All types
Hypertrophic pulm NSCLC
osteoarthropathy
SIADH SCLC (ectopic ADH production)
Cushing syndrome SCLC (ectopic ACTH production)
Eaton-Lambert SCLC
syndrome

15
 Paraneoplastic syndrome: HPOA

Syndrome characterized by:

•Excessive proliferation of skin and
bone at the distal parts of extremities,
•Digital clubbing and
•Periostosis of the tubular bones.

16
Diagnostic Investigations: Lung cancers
• Radiology

• Sputum Cytology (limited utility)

• Pleural fluid cytology

• Bronchoscopy

• Mediastinal node biopsy

• Transthoracic needle biopsy, guided by

CT
17
Bronchoscopy

18
CT-guided Transthoracic needle biopsy

19
 Small cell lung cancer (SCLC)
• Tends to be fast growing
• Usually centrally located mass
• Mostly involves hilar/mediastinal nodes
• Histology: round/fusiform cells with scanty
cytoplasm & finely granular chromatin
• Arise from neuroendocrine cells of lung &
therefore express endocrine markers.

20
Squamous Cell Ca lung
• Strong association with smoking.
• Arise centrally (hilar mass) in major
bronchi.
• Cavitation due to central necrosis.
• May arise from squamous metaplasia
or dysplasia and carcinoma in situ
(CIS) that may exist for several years
asymptomatically.
• Tumor mass obstructs major
bronchus and produces atelectasis.
• Histologic: Keratinization, keratin
pearls in a well-differentiated
squamous cell ca.
• Hypercalcemia as paraneoplastic
syndrome (because of PTHrP
secretion by tumor cells).

21
 Adenocarcinoma
• Most common form of lung cancer
• Usually Peripheral location
• Local invasion/metastasis common
• Not always associated with tobacco
• Bronchioloalveolar carcinoma (a subtype)
can present as persistent infiltrate

22
Adenocarcinoma

23
Bronchioloalveolar carcinoma (BAC)
• A subtype of adenocarcinoma
• Increasing in incidence
• Arises from peripheral parts of lung
• Solitary nodule or multiple nodules or
consolidation (diffuse pneumonic variant)
• May not destroy alveolar architecture or
stromal invasion (lepidic growth pattern)
• Least associated with cigarette smoking
• May start as an atypical adenomatous
hyperplasia (AAH) and progress to
bronchioloalveolar ca and then to invasive
adenocarcinoma in sequence.
24
 Bronchioloalveolar carcinoma growth
sequence: Radiology/ Pathology

Multiple nodules Pneumonic consolidation

AAH Grow along alveoli Invasive

(Lepidic pattern) adenocarcinoma
25
Clicker Time

26
A 56-yr-old man with no significant past medical
history presents with a seizure in the ER. Workup
shows a large central lung mass suspicious for
bronchogenic carcinoma. Lab reports a serum
osmolarity of 236 mOsm/Kg (N=290). Which
paraneoplastic syndrome is the most likely cause
of this patient’s presentation?
A. Cushing’s syndrome 20%
B. Syndrome of Inappropriate 20%
Antidiuretic Hormone
C. Hypercalcemia 20%
D. Neuropathy 20%
E. Eaton-Lambert syndrome 20%
27
37-yr-old man on a pre-employment chest x-ray
found to have a 4 cm mass on left lung. His x-ray
taken 3 yrs ago was normal. He is a non smoker.
He undergoes a biopsy and the histological
examination shows growth of malignant cells along
the alveoloar wall without invasion of the stroma.
This patient most likely has which of the following
types of lung cancer?
A. Bronchioloalveolar ca 0%
B. Adenocarcinoma 0%
C. Sqamous cell ca 0%
D. Large cell ca 0%
E. Small cell ca 0%
28
Directed Learning Activity in
Pulmonology

Topic: PLEURAL DISEASES

1
This DLA must be studied
before attending IMCQs in
Pulmonology

2
Pleural Space and Fluid

• Fluid formed by
both parietal and
visceral pleura
• Reabsorption by
pleural
lymphatics
• Normal fluid < 20
mL but turnover
may increase 25
fold.
Physiology of the Pleura and Pleural Space
• Serves as a coupling mechanism between lungs
and chest wall
• Intrapleural (intrathoracic) pressure is negative
relative to intra-alveolar and atmospheric
pressures, allowing gas exchange during
respiration
• Fluid movement is governed by Starling’s law of
transcapillary exchange
• A net pressure difference of -7 to -9 cm of H2O
favors movement of fluid into the pleural space.

4
 Pleural Effusion
Definition: ‘excess’ fluid in the pleural space.
Symptoms: Signs:
• Asymptomatic •Decreased or absent tactile
• Chest pain fremitus
•Dullness to percussion & shifting
• Dyspnea dullness (pathognomonic)
• Cough •Diminished breath sounds over
• Fever the area of effusion
•Bronchial breath sounds and
egophony can often be heard just
above the effusion due to
presence of atelectatic lung.
5
Pleural effusion: Causes (in order of
frequency)

• Congestive heart failure

• Pneumonia
• Lung malignancy
• Pulmonary Emboli
• Liver cirrhosis
• Collagen vascular diseases
• Asbestosis
• Mesothelioma

6
 Pleural Fluid: Types
Transudate Exudate
• Congestive heart • Neoplastic disease
failure • Infectious Diseases
• Cirrhosis • Pulmonary Emboli
• Nephrotic • Pancreatitis
Syndrome • Collagen Vascular
• Myxedema Diseases

Exudate if:
• Protein ratio of Pleural fl/Serum >0.5 &
• LDH ratio of Pleural fl/Serum >0.6
7
 Malignant Pleural Effusions
• Metastatic disease accounts for most
malignant pleural effusions.
• Site of origin:
– lung (men), breast (women), lymphoma,
gut, ovary
• Exudative fluid
• Mechanism of effusion: Combined effect of
 pleural permeability, Obstruction of
pleural lymphatics, Thoracic duct
interruption (chylous) and
Hypoproteinemia.
• Diagnosis: by fluid cytology or pleural
biopsy.
8
Pleural Effusion: Diagnostic tests

• Chest X-ray (PA, Lat.decubitus)

• Ultrasound
• CT Scan
• Thoracentesis: Diagnostic/Therapeutic
• Pleural biopsy

9
Thoracentesis: Superior border
Intercostal nerve block: Inferior
border

10
Approach to a Patient with a Pleural Effusion

• Nearly every patient with an unilateral pleural

effusion ‘requires’ a diagnostic thoracentesis

• A patient with bilateral pleural effusions may not

‘require’ a thoracentesis. Rule out heart failure,
nephrotic syndrome or cirrhosis in these patients.

11
 Chest radiograph: Pleural effusion

Upright chest X-ray Rt. lateral decubitus Chest

PA view: Blunting of X-ray PA view: Layering of
Rt. Costophrenic pleural effusion
angle followed by
meniscus 12
 Pleural fluid analysis
Test Significance
Red blood cells Trauma, tumor, Pulm
embolism, TB
White blood cells ↑PMN’s : Pneumonia,
pancreatitis, abd abscess
↑Lymphocytes: TB, RA &
malignancy.
Protein(Pleural/Serum) >0.5; Exudate
LDH (Pleural/Serum) >0.6 or
Pleural LDH is greater than
two-thirds of serum LDH
Cytology Tumor vs infection
13
 Diagnostic value of pleural fluid analysis:
Low glucose (<40mg/dL)
• Parapneumonic effusion (lung infection)
• Malignant pleural effusion
• Tuberculous pleural effusion
• Rheumatoid pleural effusion
• Hemothorax
• Autoimmune vasculitis (Eg., Churg-Strauss
syndrome, SLE, Dermatomyositis)

14
Diagnostic value of pleural fluid analysis:
High Amylase

• Acute pancreatic disease

• Chronic pancreatic disease
• Esophageal rupture (fluid may
contain food particles in addition)
• Malignant pleural effusion

15
 Tuberculous pleuritis: Diagnosis

• If pleural fluid adenosine deaminase

(ADA) >70 units
• If pleural fluid gamma interferon is high
• Granulomas on pleural biopsy
• Lymphocytic effusion.

16
 Chylothorax: Features
Presence of chyle in the pleural space secondary
to leakage from the thoracic duct or its
tributaries.
Diagnosis:
Rapid accumulation of fluid in pleural space
Pleural fluid is turbid post centrifugation
Measure triglycerides and cholesterol in serum
and pleural fluid. Chylothorax exists if:
– Triglycerides >110 mg/dl and
– Pleural fluid/serum triglyceride >1.0
– Pleural fluid/serum cholesterol <1.0
– Demonstration of chylomicrons in pleural fluid.
17
 Parapneumonic Effusion
• Any pleural effusion associated with infectious
pneumonia, lung abscess, or bronchiectasis
• 40% of pneumonias are associated effusion
• Character of the fluid varies from translucent,
straw-colored fluid to frank pus

Chest radiograph shows a

homogeneous opacity in
the inferior part of the left
chest, with costophrenic
angle blunting (small arrow)
and meniscus sign (large
arrow)
18
Patient:
A 30-yr-old man presents with Rt. lower chest
pain and RUQ pain. He also has minimal
cough and mild fever.
Past history: Diagnosed to have pneumonia
and received treatment 3 weeks ago.
Social history: Uses i.v. drug as well as
methadone for the past 4 years.
PE: Dull to percussion in Rt. Lower lung field
with absent breath sounds.
Imaging: CT-san shows loculated fluid in rt.
Lower lobe (next slide).
Diagnosis: Empyema due to pneumonia.
19
CT Imaging: Loculated empyema in right lung

20
 Empyema: Chest X-ray

A B
A. Right-sided empyema showing extension of the
air-fluid level to the chest wall;
B. Left-sided loculated empyema showing pleural-
based opacity (arrow) with tapering obtuse margins.
21
Patient:
A 43-yr-old man presents in the ER with a sudden
onset of dyspnea associated with right sided chest
pain. There is no history of cough, hemoptysis or
fever. No Past Medical History.
PE: Absent Tactile fremitus, Hyper-resonant
percussion note & Absent breath sounds in Rt.
lung fields.
Chest X-ray: Hyperlucency and lack of lung
markings peripheral to the linear shadow of
visceral pleura (next page).
ABG: PaO2 64, PaCO2 32, pH 7.46, HCO3 22.
CBC: Normal.
22
Diagnosis:

Right-sided
pneumothorax

23
 Pneumothorax: Pathophysiology

Note: Determinants of
pleural pressure are the
opposing recoil forces
of the lung and chest
wall.

• Normal intrapleural space is negative.

• If a communication exists between the pleural space
and either the alveoli or the atmosphere, then air will
enter the pleural space until pressures are equalized
• Result is collapse of the lung and hyper-expansion of
the hemi-thorax, leading to impairment.
24
 Pneumothorax: 3 Types

A. Spontaneous pneumothorax (SP):

❖Primary SP – without a lung disease
❖Secondary SP – with parenchymal lung disease.

B. Iatrogenic and traumatic pneumothorax: Due to

a pleural injury.

C. Tension pneumothorax: Progressive build-up of

air in pleural cavity.

25
 Pathophysiology: Spontaneous pneumothorax

Risk factors for Risk factors for

Primary Secondary
• Smoking • COPD
• Tall, thin stature • Asthma
• Marfan syndrome • TB
• Pregnancy • Sarcoidosis
• Familial pneumothorax • Cystic fibrosis
• PCP pneumonia

Mechanism: Associated Mechanism: Alveolar

with the presence of destruction associated with
asymptomatic blebs. increased pulm pressure
due to coughing. 26
 Pneumothorax: Physical Exam (Signs)

• Tactile fremitus is diminished or absent on the

affected side
• Hyper-resonance on the affected side on
percussion
• Diminished or absent breath sounds on
affected side on auscultation
• Shift of the mediastinum to the opposite side
(in case of tension pneumothorax)

27
Chest X-ray with Tension pneumothorax shows:
•Right lung is collapsed;
•Mediastinal shift to the left with compression of the left lung;
•Depressed right hemidiaphragm &
•Widening of right-sided rib spaces 28
Patient:
A 75-yr-old retired man presents with 3-month
history of chronic chest pain that is non-pleuritic,
continuous and non-radiating. He also has dyspnea
and 20 lb weight loss. There is no fever, cough or
dyspnea. He worked in an asbestos factory for 30
years.
Physical Examination:
Patient is uncomfortable at rest due to pain. His
vitals are normal.
Respiratory exam: Dull to percussion, Decreased
fremitus & Diminished breath sounds in the right
lung fields.
CT imaging: Rt. Sided nodular circumferential
pleural thickening of >1 cm (next slide). 29
CT showing rt. Sided Pleural biopsy: Shows
pleural thickening malignacy (biphasic type)

Diagnosis: Malignant Mesothelioma

30
 Malignant mesothelioma
• Associated with asbestos exposure (60%)
• Distant metastases are rare
• Tumors usually contain epithelial and
mesenchymal cells and frequently large amounts
of fibrous tissue
• Most patients present with chest pain or dyspnea
• Mostly accompanied with a unilateral exudative or
hemorrhagic pleural effusion
• Mediastinal lymph nodes may be involved
• Difficult to distinguish it from metastatic
adenocarcinoma
31
 Malignant Mesothelioma

3 histological types:
a. Epithelial type
(resembles adeno ca)
a. Sarcomatoid
b. Biphasic (a & b)

Lung covered by
mesothelioma
32
Clicker Time

33
A 26-yr-old graduate student arrives at the ER with a
sudden onset of chest pain and dyspnea. He is in
moderate distress and his resp rate is 28/min. Trachea is
central and left side is hyperresonant on percussion.
Chest auscultation shows normal breath sounds on the
right but diminished on the left chest. Which of the
following findings is most likely in his chest x-ray?

A. Opacity in the left lower lobe 0%

B. Radiolucency along the left chest 0%
wall
C. Wedge-shaped opacity in the left 0%
lung field
D. Obliteration of the left costophrenic 0%
angle
E. Hyperlucency of both lung fields 0%
34
A 61-yr-old man recently diagnosed with lung cancer
presents with a large left-sided pleural effusion.
Thoracentesis shows a milky white fluid that fails to
become clear upon centrifugation. Pleural fluid protein to
serum protein ratio is >0.5. Pleural fluid LDH to serum
LDH ratio is >0.6. Which of the following additional lab
findings is most likely of this fluid?

A. Negligible amount of Triglycerides 0%

B. Pleural fluid Triglyceride to serum 0%
triglyceride ratio is >1.0
C. Pleural fluid Cholesterol to serum 0%
cholesterol ratio is >1.0
D. Absent Chylomicrons
0%
E. High amylase content
0%
35