...

Catch the trade winds in your sails,

explore, dream, discover & live….! ”
- Mark Twain ?!*$#

“Twenty years from now

you will be more disappointed
by the things you didn't do
than by those you did.”
 Asthma
Pathophysiology

Dr. Venkatesh M. Shashidhar.

Senior Lecturer in Pathology
Fiji School of Medicine

01/11/09
Asthma-Pathology -3

Asthma:
 Chronic Inflammatory disorder of
bronchi characterized by Episodic,
reversible bronchospasm resulting
from an exaggerated
bronchoconstrictor response to
various stimuli (allergy)
 Affects 10% of children & 5%-7%
adults

Highest in NZ, Low in Fiji ~ 1% ♥
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Asthma Facts ?
 Asthma is “all in the mind.”
 You will “grow out of it.”
 Asthma can be cured,
 Not very serious disease and nobody dies from it.
 You are likely to develop asthma if someone in
your family has it.
 You can “catch” asthma from someone else who
has it.
 Moving to a different location can cure asthma.
 People with asthma should not exercise.
 Asthma does not require medical treatment.
 Medications used to treat asthma are habit-
forming.
 Someone with asthma can provoke episodes
anytime.
 Asthma can spread to other persons through
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Percent Change in Age-
Adjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
Coronary Stroke Other CVD COPD All Other
2.5 Heart Causes
Disease
2.0

1.5

1.0

0.5
–59% –64% –35% +163% –7%
0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
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Pathogenesi INDUCERS
s: Allergens,Chemical sensitisers,
Airway Air pollutants, Virus infections
Hyperresponsiveness
Genetic*

INFLAMMATION
Airflow Limitation

TRIGGERS
SYMPTOMS
Allergens, Exercise,
Cough Wheeze
Cold Air, SO2 Particulates
Dyspnoea

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Asthma Pathogenetic Types:

 Extrinsic (Allergic/Immune)
 Atopic - IgE
 Occupational - IgG
 A. Bronchopulomonary Aspergillosis -
IgE
 Intrinsic (Non immune)
 Aspirin induced
 Infections induced

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Pathogenesis - Atopic
Asthma:

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Mast cells in Asthma

Pathogenesis:

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Eosinophils in Asthma
Pathogenesis:

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Lung Morphology in Asthma

 Bronchial
inflammation
 Edema,
Mucousplugging
 Bronchospasm
 Obstruction
 Over
inflation/Atelectasis
 COPD

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Lung Hyperinflation in Asthma

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Thick bronchi with Mucous

plugs

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Mucous plug in asthma:

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Asthma - Micropathology

 Patchy necrosis of epithelium

 Sub-mucosal glandular hyperplasia
 Hypertrophy of bronchial smooth
muscle
 Eosinophils, mast cells; lympho (TH2,
CD4)
 Mucous plugs, Curschmann spirals,
 Charcot Layden crystals.
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Asthma Microscopic
Pathology

Obstructed
Inflammed
Bronchi

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Asthma - Bronchial morphology

 inflammation
 Eosinophils
 Gland
hyperplasia
 Mucous plug in
lumen
 Hypertrophy of
muscle layer

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Asthma - Bronchial morphology

 Inflammatio
n
 Mucous
Plug
 Eosinophils

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Asthma – TH2 lymphocytes

immunostaining)

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Eosinophils in Asthma:

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Curschmann's spirals:

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New Pathology & Drugs in

Asthma:
 Leukotriences - significant role in
Asthma
 Mast cells and Eosinophil - Cytokines.

 Arachidonic acid - Lipo-oxygenase –

LTD4
 Bronchospasm – Cys-LT1 receptor

 Zileuton – Lipoxygenase inhibitor

 Montelukast & zafirlukast - inhibit

CysLT1
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Cell Damage

Cell Membrane
Phospholipids
Steroids

Arachidonic
Acid Cyclooxygenas
5-Lipoxygenase
NSAID e

Prostaglandins
Leukotrienes
Prostacyclins
LTC4, D4, E4

5-LO inhibitors
Antileukotrienes
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History of Leukotrienes:
 Samuelsson et al. (1979) Stockholm
found arachidonic acid metabolites in
anaphylaxis, (SRS) called them
"leukotrienes.“ now known to be
cysteinyl leukotrienes (LT-C4, D4 and
E4).

 * Samuelsson later won the Nobel Prize

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The Reality 
 Asthma is not yet curable *
 Underdiagnosis &
Undermanagement
 Therapy is still evolving
Hope 
Better understanding of


Pathology
 New line of Promissing Drugs.

01/11/09
Proper management  normalShashi
 Thank You…

Dr. Venkatesh M. Shashidhar.

Senior Lecturer in Pathology
Fiji School of Medicine
01/11/09
Asthma-Pathology -27
Asthma Pathology - Modern
view
Allergen
Macrophage/
dendritic cell Mast cell

Th2 cell
Leukotrienes
Neutrophil
C4, D4 & E4
Eosinophil
Mucus plug
Epithelial shedding
Nerve activation

Subepithelial
fibrosis
Plasma leak
Sensory nerve
Oedema activation
Vasodilatation Cholinergic
Mucus New vessels reflex
hypersecretion
Hyperplasia Bronchoconstriction
Hypertrophy/hyperplasia

01/11/09
Barnes01/11/09
PJ Shashi
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Mast cell Degranulation

Normal 5 Seconds 60 Seconds

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Mast cell Degranulation

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Type I Hypersensitivity:

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Therapy - Pathology:

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Barnes01/11/09
PJ Shashi