asthma pa tho physiology n

8/14/2019 Asthma Pa Tho Physiology n

1/31

?!*$#

Twenty years from nowTwenty years from now

you will be more disappointedyou will be more disappointed

by the things youby the things you didn'tdidn'tdodothan by those you did.than by those you did.

...Catch the trade winds in your sails,...Catch the trade winds in your sails,explore, dream, discover &explore, dream, discover & live.! live.!

- Mark Twain


2/31

01/11/0901/11/09

AsthmaAsthma

PathophysiologyPathophysiology

Dr. Venkatesh M. Shashidhar.Senior Lecturer in Pathology

Fiji School of Medicine


3/31

01/11/0901/11/09

Asthma-Pathology -3

Shashi

AsthmaAsthma::

ChronicChronic InflammatoryInflammatorydisorder ofdisorder of

bronchi characterized bybronchi characterized by EpisodicEpisodic,,

reversiblereversiblebronchospasmbronchospasm resultingresulting

from an exaggeratedfrom an exaggerated

bronchoconstrictor response tobronchoconstrictor response to

various stimuli (various stimuli (allergyallergy))

Affects 10% of children & 5%-7%Affects 10% of children & 5%-7%adultsadults

Highest in NZ,Highest in NZ, Low in Fiji ~ 1%Low in Fiji ~ 1%


4/31

01/11/0901/11/09

Asthma-Pathology -4

Shashi

Asthma Facts ?Asthma Facts ? Asthma is all in the mind.Asthma is all in the mind. You will grow out of it.You will grow out of it. Asthma can be cured,Asthma can be cured, Not very serious disease and nobody dies from it.Not very serious disease and nobody dies from it. You are likely to develop asthma if someone inYou are likely to develop asthma if someone in

your family has it.your family has it. You can catch asthma from someone else whoYou can catch asthma from someone else who

has it.has it. Moving to a different location can cure asthma.Moving to a different location can cure asthma. People with asthma should not exercise.People with asthma should not exercise. Asthma does not require medical treatment.Asthma does not require medical treatment. Medications used to treat asthma are habit-Medications used to treat asthma are habit-

forming.forming. Someone with asthma can provoke episodesSomeone with asthma can provoke episodes

anytime.anytime.

Asthma can spread to other persons throughAsthma can spread to other persons through


5/31

01/11/0901/11/09

Asthma-Pathology -5

Shashi

Percent Change in Age-Percent Change in Age-Adjusted Death Rates, U.S.,Adjusted Death Rates, U.S.,1965-19981965-1998

0

0.5

1.0

1.5

2.0

2.5

3.0

Proportion of 1965 Rate

1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

59% 64% 35% +163% 7%

CoronaryHeart

Disease

Stroke Other CVD COPD All OtherCauses


6/31

01/11/0901/11/09

Asthma-Pathology -6

Shashi

INFLAMMATIONINFLAMMATION

Airflow Limitation

SYMPTOMS

Cough Wheeze

Dyspnoea

TRIGGERS

Allergens, Exercise,

Cold Air, SO2 Particulates

PathogenesiPathogenesi

s:s:Airway

HyperresponsivenessGenetic*

INDUCERS

Allergens,Chemical sensitisers,

Air pollutants, Virus infections


7/31

01/11/0901/11/09

Asthma-Pathology -7

Shashi

Asthma Pathogenetic Types:Asthma Pathogenetic Types:

Extrinsic (Allergic/Immune)Extrinsic (Allergic/Immune) Atopic - IgEAtopic - IgE

Occupational - IgGOccupational - IgG

A. Bronchopulomonary Aspergillosis -A. Bronchopulomonary Aspergillosis -

IgEIgE

Intrinsic (Non immune)Intrinsic (Non immune) Aspirin inducedAspirin induced Infections inducedInfections induced


8/31

01/11/0901/11/09

Asthma-Pathology -8

Shashi

Pathogenesis - AtopicPathogenesis - Atopic

Asthma:Asthma:


9/31

01/11/0901/11/09

Asthma-Pathology -9

Shashi

Mast cells in AsthmaMast cells in Asthma

Pathogenesis:Pathogenesis:


10/31

01/11/0901/11/09

Asthma-Pathology -10

Shashi

Eosinophils in AsthmaEosinophils in Asthma

Pathogenesis:Pathogenesis:


11/31


12/31

01/11/0901/11/09


Shashi

Lung Hyperinflation in AsthmaLung Hyperinflation in Asthma


13/31

01/11/0901/11/09


Shashi

Thick bronchi with MucousThick bronchi with Mucous

plugsplugs


14/31

01/11/0901/11/09


Shashi

Mucous plug in asthma:Mucous plug in asthma:


15/31

01/11/0901/11/09


Shashi

Asthma - MicropathologyAsthma - Micropathology

PatchyPatchy necrosisnecrosis of epitheliumof epithelium

Sub-mucosalSub-mucosal glandularglandular hyperplasiahyperplasia

Hypertrophy of bronchialHypertrophy of bronchial smoothsmoothmusclemuscle

EosinophilsEosinophils,, mastmast cellscells;; lympholympho (TH2,(TH2,

CD4)CD4) MucousMucous plugsplugs, Curschmann spirals,, Curschmann spirals,

Charcot Layden crystals.Charcot Layden crystals.


16/31

01/11/0901/11/09


Shashi

Asthma MicroscopicAsthma Microscopic

PathologyPathology

ObstructedInflammedBronchi


17/31

01/11/0901/11/09


Shashi

Asthma - Bronchial morphologyAsthma - Bronchial morphology

inflammationinflammation

EosinophilsEosinophils

GlandGlandhyperplasiahyperplasia

Mucous plug inMucous plug in

lumenlumen

Hypertrophy ofHypertrophy of

muscle layermuscle layer


18/31

01/11/0901/11/09


Shashi

Asthma - Bronchial morphologyAsthma - Bronchial morphology

InflammatioInflammatio

nn

MucousMucous

PlugPlug EosinophilsEosinophils


19/31

01/11/0901/11/09


Shashi

Asthma TH2 lymphocytesAsthma TH2 lymphocytes

immunostaining)immunostaining)


20/31

01/11/0901/11/09


Shashi

Eosinophils in Asthma:Eosinophils in Asthma:


21/31

01/11/0901/11/09


Shashi

Curschmann's spirals:Curschmann's spirals:


22/31

01/11/0901/11/09


Shashi

New Pathology & Drugs inNew Pathology & Drugs in

Asthma:Asthma:

Leukotriences - significant role inLeukotriences - significant role in

AsthmaAsthma

Mast cells and Eosinophil -Mast cells and Eosinophil - CytokinesCytokines..

Arachidonic acid -Arachidonic acid - Lipo-oxygenaseLipo-oxygenase

LTD4LTD4

Bronchospasm Bronchospasm Cys-LT1Cys-LT1 receptorreceptor ZileutonZileuton Lipoxygenase inhibitor Lipoxygenase inhibitor

MontelukastMontelukast && zafirlukastzafirlukast - inhibit- inhibit

CysLT1CysLT1


23/31

01/11/0901/11/09


Shashi

ArachidonicAcid

Leukotrienes

LTC4, D4, E4

Cyclooxygenase5-Lipoxygenase

Prostaglandins

Prostacyclins

Cell Damage

Cell MembranePhospholipids

5-LO inhibitors

Antileukotrienes

Steroids

NSAID


24/31

01/11/0901/11/09


Shashi

History of Leukotrienes:History of Leukotrienes:

Samuelsson et al. (1979) StockholmSamuelsson et al. (1979) Stockholm

found arachidonic acid metabolites infound arachidonic acid metabolites in

anaphylaxis, (SRS) called themanaphylaxis, (SRS) called them

"leukotrienes. now known to be"leukotrienes. now known to becysteinyl leukotrienes (LT-C4, D4 andcysteinyl leukotrienes (LT-C4, D4 and

E4).E4).

* Samuelsson later won the* Samuelsson later won theNobel PrizeNobel Prize

25


25/31

01/11/0901/11/09


Shashi

The RealityThe Reality Asthma is not yet curable *Asthma is not yet curable *

Underdiagnosis &Underdiagnosis &

UndermanagementUndermanagement

Therapy is still evolvingTherapy is still evolving

HopeHope Better understanding ofBetter understanding of

PathologyPathology

New line of Promissing Drugs.New line of Promissing Drugs.

Pro er mana ementPro er mana ement normalnormal


26/31

01/11/0901/11/09

Thank YouThank You

Dr. Venkatesh M. Shashidhar.Senior Lecturer in Pathology

Fiji School of Medicine

A h P h l 27


27/31

01/11/0901/11/09


Shashi

Asthma Pathology - Modernview

Barnes PJ

Allergen

Mucus

hypersecretion

Hyperplasia

Vasodilatation

New vessels

Plasma leak

Oedema

Bronchoconstriction

Hypertrophy/hyperplasia

Cholinergicreflex

Subepithelial

fibrosis

Sensory nerveactivation

Eosinophil

Mast cell

Th2 cell Neutrophil

Macrophage/

dendritic cell

Mucus plugEpithelial shedding

Nerve activation

Leukotrienes

C4, D4 & E4

A th P th l 28


28/31

01/11/0901/11/09


Shashi

Mast cell Degranulation

Barnes PJ

Normal 5 Seconds 60 Seconds

A th P th l 29


29/31

01/11/0901/11/09


Shashi

Mast cell Degranulation

Barnes PJ

A th P th l 30


30/31

01/11/0901/11/09


Shashi

Type I Hypersensitivity:

Barnes PJ

A th P th l 31


31/31

01/11/0901/11/09


Sh hi

Therapy - Pathology:

asthma pa tho physiology n

Documents