...
Catch the trade windsin 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
02/25/16
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
02/25/16
Shashi
Asthma-Pathology -4
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 caughing.
Asthma is born with you. Familial/genetic.
02/25/16
Shashi
Asthma-Pathology -5
Percent Change in AgeAdjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
2.5
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
59%
64%
35%
+163%
7%
2.0
1.5
1.0
0.5
0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
02/25/16
Shashi
Asthma-Pathology -6
Pathogenesi
s:
Airway
Hyperresponsiveness
Genetic*
INDUCERS
Allergens,Chemical sensitisers,
Air pollutants, Virus infections
INFLAMMATION
Airflow Limitation
TRIGGERS
Allergens, Exercise,
Cold Air, SO2 Particulates
02/25/16
SYMPTOMS
Cough Wheeze
Dyspnoea
Shashi
Asthma-Pathology -7
Asthma Pathogenetic Types:
Extrinsic (Allergic/Immune)
Atopic - IgE
Occupational - IgG
A. Bronchopulomonary Aspergillosis IgE
Intrinsic (Non immune)
Aspirin induced
Infections induced
02/25/16
Shashi
Asthma-Pathology -8
Pathogenesis - Atopic Asthma:
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Asthma-Pathology -9
Mast cells in Asthma
Pathogenesis:
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Asthma-Pathology -10
Eosinophils in Asthma
Pathogenesis:
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Asthma-Pathology -11
Lung Morphology in Asthma
02/25/16
Bronchial
inflammation
Edema,
Mucousplugging
Bronchospasm
Obstruction
Over
inflation/Atelectasis
COPD
Shashi
Asthma-Pathology -12
Lung Hyperinflation in Asthma
02/25/16
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Asthma-Pathology -13
Thick bronchi with Mucous
plugs
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Asthma-Pathology -14
Mucous plug in asthma:
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Asthma-Pathology -15
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-Pathology -16
Asthma Microscopic Pathology
Obstructed
Inflammed
Bronchi
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Asthma-Pathology -17
Asthma - Bronchial morphology
02/25/16
inflammation
Eosinophils
Gland
hyperplasia
Mucous plug in
lumen
Hypertrophy of
muscle layer
Shashi
Asthma-Pathology -18
Asthma - Bronchial morphology
02/25/16
Inflammatio
n
Mucous
Plug
Eosinophils
Shashi
Asthma-Pathology -19
Asthma TH2 lymphocytes
immunostaining)
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Asthma-Pathology -20
Eosinophils in Asthma:
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Asthma-Pathology -21
Curschmann's spirals:
02/25/16
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Asthma-Pathology -22
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
02/25/16
Shashi
Asthma-Pathology -23
Cell Damage
Cell Membrane
Phospholipids
5-Lipoxygenase
Steroids
Arachidonic
Acid
Cyclooxygenas
e
NSAID
Leukotrienes
Prostaglandins
LTC4, D4, E4
Prostacyclins
5-LO inhibitors
Antileukotrienes
02/25/16
Shashi
Asthma-Pathology -24
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
02/25/16
Shashi
Asthma-Pathology -25
The Reality
Asthma is not yet curable *
Underdiagnosis &
Undermanagement
Therapy is still evolving
Hope
Better understanding of Pathology
New line of Promissing Drugs.
Proper management normal life.
02/25/16
Shashi
Thank You
Dr. Venkatesh M. Shashidhar.
Senior Lecturer in Pathology
Fiji School of Medicine
02/25/16
Asthma-Pathology -27
Asthma Pathology - Modern
Allergen
view
Macrophage/
dendritic cell
Th2 cell
Mast cell
Leukotrienes
C4, D4 & E4
Neutrophil
Eosinophil
Mucus plug
Nerve activation
Epithelial shedding
Subepithelial
fibrosis
Plasma leak
Oedema
Mucus
hypersecretion
Hyperplasia
02/25/16
Barnes02/25/16
PJ
Vasodilatation
New vessels
Sensory nerve
activation
Cholinergic
reflex
Bronchoconstriction
Hypertrophy/hyperplasia
Shashi
Asthma-Pathology -28
Mast cell Degranulation
Normal
02/25/16
Barnes02/25/16
PJ
5 Seconds
60 Seconds
Shashi
Asthma-Pathology -29
Mast cell Degranulation
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Barnes02/25/16
PJ
Shashi
Asthma-Pathology -30
Type I Hypersensitivity:
02/25/16
Barnes02/25/16
PJ
Shashi
Asthma-Pathology -31
Therapy - Pathology:
02/25/16
Barnes02/25/16
PJ
Shashi
