Random - pruritus, structure function, psychoneuroderm Flashcards
What substances work as pruritogens in atopic dermatitis through activation of protease-activated receptor-2 nerve endings in skin?
trypsin, tryptase, cathepsins, kallikreins
Release of histamine from mast cells in what portion of the skin leads to urticaria?
upper dermis –> causes wheal and flare & itch
Release of histamine from mast cells in what portion of the skin leads to angioedema?
deep dermis or subcutaneous tissue –> accompanied by pain rather than itch
What are the three groups of primary sensory nerves?
A(beta), A(delta), and C nerves
Which group(s) of primary sensory nerves is/are involved in the conduction of thermal and pain/itch sensation?
A(delta) and C nerves
Which group(s) of primary sensory nerves is/are involved in the conduction of tactile sensation?
A(beta), A(delta), and C nerves
The first pain from the skin surface is described as stabbing and is conducted by what primary sensory nerve(s)?
A(delta)
The second pain from the skin surface is described as “burning” and is conducted by what primary sensory nerve(s)?
C nerves
Do mu-opioid receptor agonists induce or inhibit itch?
induce – histamine-independent and antihistamine-resistant
Do kappa-opioid receptor agonists induce or inhibit itch?
inhibit – can inhibit morphine-induced itch as well as other subtypes of itch
To what receptor does substance P bind with greatest affinity?
Neurokinin-1 receptor – expressed in both the peripheral and central nervous systems
What neurotrophins can keratinocytes release that can directly activate itch fibers in the skin OR activate mast cells to release pruritogenic mediators?
nerve growth factor**, neurotrophin-4, lipid mediators, endothelin-1
What substance do keratinocytes release that can bind to inhibitory receptors on sensory nerves?
endocannabinoids
T/F: Pruritus can be induced via binding of histamine to H1 receptors on nerve fibers.
True - although this does not seem to be a major pathway of itch induction
Give examples of mast cell activators in pruritic diseases.
neuropeptides - vasoactive intestinal peptide, calcitonin gene related peptide, substance P** and endothelin-1**
T/F: Eosinophils in atopic skin can contribute to enhanced levels of nerve growth factor.
TRUE
In the skin, pruritus is mediated by free nerve endings of non-myelinated nerve fibers located where?
dermoepidermal junction and within the epidermis
How does scratching provide relief from pruritus?
pruritus can be suppressed or obscured by pain stimuli
What is peripheral sensitization and how does it relate to pruritus?
chronic stimulation of neuroreceptors can lead to a reduction in the stimulus threshold of the receptors
The gastrin-releasing peptide receptor is exclusively responsible for transmitting the perception of what?
pruritus – NOT pain or temperature
What is pruriceptive pruritus?
originates directly in the skin as a consequence of dermatoses – transmitted through C fibers
What is neuropathic pruritus?
caused by damage of the itch-transmitting afferents of the peripheral nerves or the spinal cord
What is neurogenic pruritus?
caused directly by diseases of central structures of the CNS – such as brain tumors or abscesses
What is psychogenic pruritus?
based on metabolic disorders in the CNS (e.g. tactile hallucinations, delusional state of parasitosis)
What is the most often cause of pruritus of primarily noninflamed skin?
systemic diseases (e.g. cholestatic liver disease, chronic renal insufficiency, diabetes mellitus, iron deficiency, haematological pruritus, neoplasms, lymphoma)
T/F: Topical antihistamines are effective in controlling histamine-induced itch.
False - have no antipruritic effect and can have a sensitizing effect
_____ is a TETRAcyclic antidepressant with additional H1 antihistaminic action and a serotonergic effect.
Mirtazapine
To what receptor does capsaicin bind? What is the effect?
transient receptor potential - vanilloid (TRPV1); administration of capsaicin excites but then desensitizes sensory afferents via TRPV1 activation
What effect does IFN-gamma have on pruritus: inhibit or induce?
inhibits
What antibiotic class reduces PAR-2-mediated production of IL-8 in keratinocytes?
tetracyclines
What is the main source of nerve growth factor in the skin?
keratinocytes and mast cells
What Th2 cytokines have been shown to directly induce itch?
IL-4, IL-13, IL-31, IL-33, TSLP
Allergic contact dermatitis involves what type of immune response?
type IV hypersensitivity reaction; relies on a Th1 response to an antigen by an antigen-presenting cell
What is the main difference between irritant contact dermatitis and allergic contact dermatitis?
ACD is an antigen-specific reaction to an allergenic irritating agent whereas ICD is not antigen-specific
Irritant contact dermatitis is thought to directly damage keratinocytes which leads to release of what?
IL-1alpha
Cytokines such as IL-1alpha, IL-1beta, TNF-alpha, GM-CSF, IL-6, and IL-8 produced during an irritant contact reaction have what effect on the dermis?
Langerhans cells migrate to the dermis and fibroblasts are stimulated to produce collagenases and prostaglandin E
What cells are the main mediators of skin lesions with allergic contact dermatitis?
Cytotoxic CD8+ T lymphocytes
What are the phases of allergic contact dermatitis?
1) Sensitization phase, 2) Elicitation phase - immune system triggers and antigen-specific response upon re-exposure to the sensitizer
T/F: Irritant contact dermatitis and allergic contact dermatitis can happen concurrently.
True - most sensitizers are also irritants – the sensitization phase of ACD can be associated with the clinical signs of ICD
What is the skin homing marker present on memory T cells?
cutaneous lymphocyte antigen
What cytokine do sensitizer-specific cytotoxic T cells release? What is its function in allergic contact dermatitis?
IFN-gamma –> activates keratinocytes –> upregulation of adhesion molecules and cytokines/chemokines –> further recruitment of T cells, NK cells, macrophages, mast cells, and/or eosinophils to the site of hapten exposure
What is different about the distribution of lesions with irritant contact dermatitis and allergic contact dermatitis?
lesions from ICD typically develop only in the area of direct contact (well-demarcated); lesions of ACD may extend beyond the area of contact and therefore are less well defined
Lesions associated with allergic contact dermatitis?
vesicles
Lesions associated with irritant contact dermatitis?
ulceration and epidermal necrosis
What is the gold standard diagnostic test for allergic contact dermatitis?
patch testing
Are topical medications such as neomycin or propylene glycol more likely to be irritants or allergens?
allergens
Where is the stratum lucidum found in dogs and cats?
footpads and nasal planum
What hormones affect pigmentation?
alpha-MSH and beta-lipotropin from the pituitary gland
What are the functions of Merkel’s cells in the skin?
slow-adapting mechanoreceptors; may have roles in controlling hair follicle activity, cutaneous blood flow, sweat production, and keratinocyte proliferation
Where are Merkel’s cells located?
stratum basale, tylotrich pads, hair follicle epithelium