UNPAR PATOFISIOLOGI GATAL
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Transcript of UNPAR PATOFISIOLOGI GATAL
7/23/2019 UNPAR PATOFISIOLOGI GATAL
http://slidepdf.com/reader/full/unpar-patofisiologi-gatal 1/14
ITCH
PATHOPHYSIOLOGY
Ninik Sukartini
Clinical Pathology Dept. FMUI
7/23/2019 UNPAR PATOFISIOLOGI GATAL
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INTRODUCTION
• Itch is the principal symptomof sin !isease an! is an
important sin manifestationof systemic !isease"
• Ho# !oes scratchin$temporarily relie%e itch &
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introduction
• Classifcation o itch : – Pr'ritocepti%e : generated in the skin usually
y an in!a""atory or other #isile pathologicalprocess eg scaies$ urticaria
– Ne'ro$enic : generated in the CNS in responseto circulating pruritogens as in cholestasis
– Ne'ropathic : due to anato"ical lesions o thecentral or peripheral ner#ous syste"s eg ner#e
entrap"ent$ tu"our – Psycho$enic : including delusional parasitosis
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Itch receptors
• %pider"is &especially keratinocytes'constitute the itch receptor
• (eratinocytes e)press a range o
ne'ropepti!e me!iators and receptors *hich in#ol#ed in pruritus
• Mediators : opioids$ ner#e gro*th actor&N+F'$ sustance P
• ,eceptors: #anilloid receptors$ proteinaseacti#ated receptor type - &P,-'$ #oltage/gated 0P channel
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Neural path*ay or itch
• Slo#(con!'ctin$ 'nmyelinate! C ne'rons *hich only trans"it itch &and te"peraturechanges' in response to hista"ine
• ,epresent only aout 1 2 o total neurons
• Selecti#ely acti#ated in the chronic pruriticskin disease
• Contralateral transmission ne'rons$
consist o an itch/specifc suclass o la"ina 3spinothala"ic tract neurons$ con#ey itch tothe thala"us
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,egulation o itch• Inhi)itory ne'ronal circ'it located in the
sustantia gelatinosa o the posterior horns ospinal cord a $ate! mechanism *hereya4erent itch can e regulated
• Increased tone in descending path*ay results
ro" #isual$ auditory and other sti"uli acti#ation o inhiitory neuronal circuit closureo the gated "echanis" di"inished itch tra5c
reason !'rin$ !aytime* itch is less
tro')lesome• ,esult o an i"alance et*een opioid actions
on central 6 &increasing itch' and κ &di"inishingitch' receptors
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Mediators o itch
• Cross(tal )et#een C ne'ron terminals an!the spatially closely relate! !ermal mast
cells
• 7ista"ine
%icosanoids ligates 73 receptors associated
0NF/8 *ith C neuron
• 0ryptase acti#ate P,- e)pressed on a4erent
C neuron ter"inals
sti"ulates itch sensation9 triggers release o sustance P urther"ast cell acti#ation
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Mediators o itch
• Ne'rotrophins +NG,- causesprolieration o un"yelinateda4erent ner#e ter"inals$
sensitisation o a4erent ner#eter"inals and increased e)pressiono neuropeptides
• (eratinocytes e)press high le#el oN+F
• 7igh urinary and plas"a le#el o N+F
ound in patient *ith atopic ece"a
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Ho# !oes scratchin$ temporarily relie%e itch &
• Scratching acti#ates thickly
"yelinated ast/conducting ;neurons *idespread surroundinhiition to acti#ation o theInhi)itory ne'ronal circ'it
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Itch o cholestasis
• <pioids cause intense pruritus
• =iliary ostruction leads to increasedintrahepatic synthesis o opioidpeptides *hich spill o#er in to thecirculation and cause pruritus yacting on 6/opioid receptors in
central ner#ous syste"
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Than yo'