viewpoint in leptospirosis - ministry of public...

VIEWPOINT IN LEPTOSPIROSIS

VISITH SITPRIJA

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LEPTOSPIROSIS : DIRECTION

•• TemperatureTemperature•• OsmolalityOsmolalityOsmolalityOsmolality•• ElectrolytesElectrolytes•• pHpH•• TaxonomyTaxonomy--GenomeGenomeLeptospires •• TaxonomyTaxonomy--GenomeGenome

P t tP t t

Animals Man

•• Prevent entryPrevent entry•• VaccineVaccine•• Early diagnosisEarly diagnosisAnimals Man •• Early treatmentEarly treatment

DiseaseDisease Non diseaseNon disease

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PathophysiologyPathophysiology TreatmentTreatment

ION CHANNEL FUNCTION

Immunity

Neuromuscular function

T itt d hTransmitters and hormones

Cell volume regulationCell volume regulation

Cell growth

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CaCa Na Na NaKNaK-- ATPaseATPase

NaNaCaCa KK KK KKENaCENaC CaCa

NaNa

KKVV KKATPATP KKCaCaKKKK

NaNaHH

NHENHE ClClHCOHCO33

ClClNaNa

ClCl NaNa KKClClCFTRCFTR AQPAQPClCl ClCl

NCCNCC

NaNa KK

NKCLNKCL

CFTRCFTRCaCCCaCC AQPAQP

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NCCNCC NKCLNKCL

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INFLAMMATION - HYPOXIA

Loss of polarity

Channel dysfunction

Di ti f ll l j tiDisruption of cellular junction

Channel openingp g

Cell swelling

Cell death

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RESPIRATORY SYSTEM

Channels Cytokines

ENaC* TNF IL 1 TGF IL 4ENaC* TNF, IL-1β, TGFβ1, IL-4

NKCC*

CFTR IFNγ, TGF

CFTR IL-1, IL-4

AQPAQP1, 5

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GASTROINTESTINAL TRACT

Channels Cytokines

CFTR IL-1β, IL-3, TNF, Subs.P

ENaC TNF IL 1 IFNγENaC TNF, IL-1, IFNγ

NKCC TNF, IFNγγ

NaK-ATPase TNF, IFNγ, TGF

APQ2, 3

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KIDNEY Channels Cytokines

ENaC Bradykinin

NKCC*NKCC*

NaK-ATPase Bradykinin, IL-1β, NO, PGE2NaK ATPase Bradykinin, IL 1β, NO, PGE2

AQP2*

NHE*

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INFECTION

Modulation of ion channelsModulation of ion channels

Role of cytokines and mediators

Severity of infection

S f fSpecificity of toxin

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