PHSL 233 - LECTURE 21

What is acute inflammation and itch triggered by

• foreign bodies

• burns

• frostbite

• UV

• chemical irritants

• 
  

how long does an itch response/acute inflammation ladt

• minutes to days

how do keratinocytes detect invasion and damage

• pattern recognition receptors recognsie damage associated molecular patterns and pathogen associated molecule patterns

what do activates keratinocytes do

• intiate inflammation by releasing cytokines, chemokines and antimicrobial peptides

what are some of the things that keratinocytes release to initiate inflammation

• interlukin 8

• interleukin 1

• Thymic stromal lymphopoietin

• antimicrobial peptide

what does interleukin 8 released by keratinocytes do

• recruits neutrophils

what does interleukin 1 released by keratinocytes do

• activates inflammatory cells

what does thymic stromal lymphopoietin released by keratinocytes do

• activates itch pathways

what does antimicrobial peptide released by keratinocytes do

• kills microbes

other than keratinocytes, what other cells in the skin detect trouble

• mast cells through patern recognition receptors and antibodies (produced in response to primary exposure)

what do activated mast cells do

• intiate itch and inflammation by releasing signals

• histamines

• proteases

• leukotrines

• prostaglandins

• TNF

what does histamine do when released by mast cells

• induces vasodilates

• increases vascular permeability

• stimulates itch response

what do proteases do when released by mast cells

• tissue remodelling

• activation of inflammatory pathways

what does TNF do when released by mast cells

• tumour necrosis factor

• activates endothelial cells

• recruits leukocytes

what do leukotrines and prostaglandins do when released by mast cells

• activates:

• vascular pathways

• inflammatory pathways

• itch pathways

overall what are the two major responses produces in response to skin damage/invasion

• itch

• inflammation

what is the very first response to detection of damage/invasion (as part of inflammatory response)

• keratinocytes and mast cells release mediators which produce 3 main responses

• endothelial activation

• increased vascular permeability

• vasodilation

what activates endothelial cells

• interleukin 1

• TNF

• pamps

what induces expression of adhesion moleculkes

• NF-kb signaling

what recruits leukocytes

• chemokines provide gradient

• adhesion molecules provide attachment points

• allows leukocytes to be drawn to and adhere to inflamed skin

what increases vascular permeability

• histamine

• causes contraction and junction seperation

what causes edema

• histamine increases vascular permeability which alows plasma proteins to enter the skin through endothelial gaps

what promotes vasodilation

• histamine stimulates nitric oxide production which causes smooth musce to relax

• blood flow increases

what causes warmth and redness in inflamed skin

• vasodilation

• increased blood flow

what are pruriceptors

itch receptors

expressed on free sensory nerve endings in the skin

what activates prurieceptors

histamine and cytokines

what does activation of pruriceptors generate

• nerve impulses transmitted to the brain and spinal cord

• perception of itch triggers scratching response

what is acute itch triggered by

• histamine

what is chronic itch triggered by

TSLP - thymic stromal lymphopoietin

IL-31

what is a cause of acute itch

• bite

what is a cause of chronic itch

eczema

how long does chronic itch last for

weeks to months

how long does acute itch last

• minutes to hours

is antihistamine effective against acute and chronic itch

• no

• only effective against acute itch

describe the itch signalling pathway

• mediators bind to ion channels in sensory nerves

• sodium and calcium enter the neuron

• membrane depolarises

• AP generates

• itch signal travels to CNS

what does scratching activate

• nociceptors

what are nociceptors

• pain receptors

why does scratching feel good

• perception of pain due to activation of pain receptors provides temporary relief from itch

• neurotransmitters that are produce induce pain and suppress itch

describe the itch-scratch cycle

• scratching damages the skin barrier

• barrier damage releses more DAMPs

• keratinocytes and mast cells release more inflammatory mediators

• itch response increases

• cycle repeats

what are the ways the itch-scratch cycle can be broken

• antihistamines

• corticosteroids

• barrier creams

describe how antihistamines break the itch-scratch cycle

block histamine pathways preventing activation of itch receptors

describe how corticosteroids break the itch-scratch cycle

• suppress the cytokine pathways preventing activation of itch receptors

describe how barrier creams break the itch-scratch cycle

• block trigger entry which allows the skin barrier to heal

• act as a temporary barrier

what is pruritis

• chronic itch

• can be triggered by infectious or systemic disease

• persists for weeks to months