...

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:

02/25/16

Shashi

Asthma-Pathology -9

Mast cells in Asthma

Pathogenesis:

02/25/16

Shashi

Asthma-Pathology -10

Eosinophils in Asthma
Pathogenesis:

02/25/16

Shashi

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

Shashi

Asthma-Pathology -13

Thick bronchi with Mucous

plugs

02/25/16

Shashi

Asthma-Pathology -14

Mucous plug in asthma:

02/25/16

Shashi

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.

02/25/16

Shashi

Asthma-Pathology -16

Asthma Microscopic Pathology

Obstructed
Inflammed
Bronchi

02/25/16

Shashi

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)

02/25/16

Shashi

Asthma-Pathology -20

Eosinophils in Asthma:

02/25/16

Shashi

Asthma-Pathology -21

Curschmann's spirals:

02/25/16

Shashi

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

02/25/16

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