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
What are the functions of cutaneous nerves?
1) Sensory perception (touch, heat, cold, pressure, pain, itch); 2) Modulation of inflammation, proliferation, wound healing via neuropeptide activation of target cells (keratinocytes, mast cells, endothelial cells); 3) Control vasomotor tone; 4) Control piloerection; 5) Influence secretory activities of glands
List neuropeptides produced by cutaneous nerves.
1) Substance P, 2) Neurokinin A, 3) Calcitonin gene-related peptide, 4) Vasoactive intestinal peptide, 5) Neuropeptide Y, 6) Somatostatin, 7) Pituitary adenylate cyclase activity peptide
List the types of mechanoreceptors found in the skin
1) Pacinin corpuscle units; 2) Meissner’s or Ruffini corpuscles; 3) Afferent units sensitive to hair movement; 4) Slow-adapting type I endings from Merkel cell complexes; 5) Slow-adapting type II units associated with Ruffian endings; 6) delta High-threshold mechanoreceptor units (A-delta axons); 7) Polymodal nociceptor units with C axons
What does a Pacinian corpuscle unit detect?
vibration and pressure
What do Meissner’s and Ruffini corpuscles detect?
sensitive to the velocity of skin movement or touch
What activates slow-adapting type I endings from Merkel cell complexes?
steady pressure
What activates slow-adapting type II units associated with Ruffian endings?
skin stretch
What do A-delta axons transmit in the skin? Are they slow or fast? Myelinated or unmyelinated?
respond to painful stimuli and carry signals for spontaneous itch (well-localized, prickling); conduct rapidly, myelinated
What do C axons transmit in the skin? Slow or fast? Myelinated or unmyelinated?
hyperalgesia and itch; slow-conduting, unmyelinated, and transmit a diffuse burning itch sensation
Where are sinus hairs (vibrissae, whiskers) located?
muzzle, lip, eyelid, face, throat, palmar aspect of carpus in cats (pili caralis)
Where are tylotrich hairs located?
scattered among ordinary body hairs, associated with a tylotrich pad
Are sinus hairs fast or slow adapting mechanoreceptors?
slow-adapting mechanoreceptors
Are tylotrich hairs fast or slow adapting mechanoreceptors?
rapid-adapting mechanoreceptors – the touch plaques serve as slow-adapting touch receptors
Describe a tylotrich hair
hair follicle is larger than surrounding ones and contains a single stout hair; an annular complex of neurovascular tissue surrounds the follicle at the level of the sebaceous gland. These hairs are located on a tylotrich pad consisting of the hair follicle and an underlying convex area of fine highly vascularized connective tissue. Unmyelinated nerve fibers ending as flat plaques (touch plaques) in association with Merkel’s cells are also located on the pad
Describe a sinus hair
These hairs are thick and stiff and are characterized by an endothelium-lined blood sinus located between the external root sheath of the follicle and an outer connective tissue capsule. Pacinian corpuscles are located close to the sinus hair follicle.
What are the three major vascular plexuses of the skin and what do they supply?
1) Superficial plexus - located immediately below the epidermis, capillary loops from this plexus supply the epidermis and the upper portions of hair follicles; 2) Middle plexus - located at level of sebaceous glands, gives off branches to the arrector pili muscles, ascending branches that supply superficial plexus, and ascending and descending branches that supply the middle portion of the hair follicles and sebaceous glands; 3) Deep plexus - found at interface of dermis and subcutis, branches descend into subcutis and ascend to supply lower portions of the hair follicles and the epitrichial sweat glands, ascending vessels continue upward to supply the middle plexus
What are the functions of cutaneous lymph vessels?
1) return protein, fluid, and cells from the interstitial spaces to the bloodstream; 2) Remove material that has penetrated the epidermis and dermis (solvents, medications, vaccines, other antigens). 3) Link the skin and regional lymph nodes and thus function in immunoregulation.
What are telangiectasias?
small, dilated, superficial blood vessels that blanch with diascopy – most commonly associated with HAC (also dermatomyositis and CLE)
Differentiate between hyperkeratosis and lichenification
hyperkeratosis - increase in the thickness of the stratum corneum; lichenification - marked thickening of all layers of the epidermis
What is the difference between a fistula and a sinus?
fistula - abnormal passage between two organs or between a structure and a body surface; sinus - tract leading from a suppurative cavity to the skin surface (type of fistula)
Appearance of macroconidia of Trichyophyton mentagrophytes
Only found occasionally. Are cigar shaped, thin walled with narrow attachment to the hyphae
Appearance of macroconidia of Microsporum gypseum
Spindle-shaped with thin walls and rounded ends. Contains less than six cells**
Appearance of macroconidia of Microsporum canis
Spindle-shaped with ThICK walls and knobs at the ends. Contains more than 6 cells
What does the first jar of DiffQuik contain?
95% alcohol
What does the second stain of DiffQuick contain?
xanthene dye – stains cells and organisms red
What does the third stain of DiffQuick contain?
buffered thiazine dye – stains cells and organisms purple
Examples of mediators of pruritus
- Histamine, 2. Endopeptidases (trypsin, papain, kallikrein), 3. Prostaglandins (E series and endoperoxidases), 4. Endogenous opioid peptides, 5. Substance P
How do Prostaglandins induce pruritus?
potentiating release of proteases from keratinocytes and leukocytes; lower threshold and increasing duration of histamine-induced pruritus
How do endogenous opioid peptides induce pruritus?
potentiate pre-existing pruritus; opiate antagonist naloxone HCl has an attenuating effect on the histamine-induced component of pruritus
T/F: Pruritus is a minor sensation in comparison with the sensations of heat, cold, touch, and pain.
True - local application of a competing stimulus to a pruritic area often suppresses the pruritic sensation
A change in neuronal output to a constant sensory input
Adaptation
Touch-evoked pain
Allodynia
Touch-evoked itch, itchy skin
Alloknesis
Epicritic Itch
Itch that is sharp and well localized; trasnmitted by A-delta fibers (myelinated) at ~10-20 m/s (rapid)
Hyperalgesia
Increased sensitivity to pain stimulus
Hyperknesis
Increased sensitivity to pruritic stimulus
Mechanotransduction
conversion of a force into a cellular signal
Nociceptor
somatosensory neuron activated by noxious mechanical, thermal, or chemical stimuli
Protopathic itch
Itch that is poorly localized and may have a burning quality; transmitted by C fibers (nonmyelinated) at ~2 m/s (slow)
Pruriceptor
Somatosensory neuron activated by pruritic stimuli
Punctuate hyperkinesis
Skin prick inducing intense itch sensation
Rapid-adapting receptor
Light-touch receptor that responds robustly at the onset of a sustained mechanical stimulus
Slow-adapting receptor
Light-touch receptor that fires at a low level throughout a sustained mechanical stimulus
Threshold
amount of stimulus necessary to evoke a response
Meissner corpuscle: Rapid or Slow-adapting mechanoreceptor? Location? What is its stimulus?
Rapid-acting mechanoreceptor
Located in superficial dermis, layers of cells enfold the large leaflike endings of 2-6 afferent nerves
Responds to vibration
Merkel cell: Rapid or Slow-adapting mechanoreceptor? Location? Stimulus?
Slow-adapting Type I mechanoreceptor
Located in basal layer of epidermis, unmyelinated ending of afferent nerve
Touch receptor, responds to pressure, edges, and curves
Pacinian corpuscle: Rapid- or slow-adapting mechanoreceptor? Characteristics? Stimulus?
Rapid-adapting mechanoreceptor
Large, layered, onion-like structure enclosing an afferent neuron
Sensitive to pressure and vibration
Ruffini corpuscle: Rapid- or slow-adapting mechanoreceptor? Location? Stimulus?
Slow-adapting Type II mechanoreceptor
Located in connective tissue of dermis; large spindle-shaped structure interconnects with collagen matrix
Sensitive to skin stretch
Sinus hairs (vibrissae, whiskers): Rapid- or slow-adapting mechanoreceptors? Characteristics? What else is located near sinus hair follicles?
Slow-adapting mechanoreceptors
Longer, thicker, and stiffer than normal hairs and have an endothelium-lined blood sinus located between the external root sheath of the follicle and the outer connective tissue capsule
Pacinian corpuscles are located close to the sinus hair follicle
Tylotrich hair: Rapid- or slow-adapting mechanoreceptor? Characteristics? What else is associated with it?
Rapid-adapting mechanoreceptor
Specialized hair that is a large primary follicle surrounded by a ring of neurovascular tissue
Associated with a tylotrich pad
Tylotrich pad: Rapid- or slow-adapting mechanoreceptor? Characteristics?
Slow-adapting mechanoreceptors
Local area of epidermal thickening with a layer of highly vascular and well-innervated connective tissue under it
Acetylcholine: Role in inflammation?
Keratinocyte differentiation and function, regulation of skin circulation, sweat gland secretion
Calcitonin gene-related peptide: Role in inflammation?
Keratinocyte and endothelial cell proliferation, stimulates cytokine production
Neurokinin A: Role in inflammation?
Upregulates keratinocyte expression of NGF
Noradrenaline: Role in inflammation?
Innervation of blood vessels, arrector pili muscles
Affects activity of NK cells, monocytes, lymphocytes
Inhibits keratinocyte migration
Pituitary adenylate cyclase-activating polypeptide: Role in inflammation?
Vasdilation, immunomodulation, nociception
Pro-opiomelanocortin: Role in inflammation?
Immunomodulation (decreases inflammation)
Substance P: Role in inflammation?
Inflammation, upregulation of cell adhesion molecules
Vasoactive intestinal peptide: Role in inflammation?
Vasodilation, proliferation and migration of keratinocytes, histamine release from mast cells
Acetylcholine: Source?
Autonomic cholinergic nerves, keratinocytes, lymphocytes, melanocytes, fibroblasts, endothelial cells
Acetylcholine: Receptor?
Nicotinergic and muscarinergic ACh receptors
Calcitonin gene-related peptide: Source?
sensory nerve fibers
Calcitonin gene-related peptide: Receptor?
Calcitonin gene-related peptide receptor
Neurokinin A: Source?
Sensory nerve fibers
Neurokinin A: Receptor?
Tachykinin receptors
Noradrenaline: Source?
sympathetic nerves, keratinocytes, melanocytes
Noradrenaline: Receptors?
Adrenergic receptors
Pituitary adenylate cyclase-activating polypeptide: Source?
Autonomic and sensory nerves, lymphocytes, endothelial cells
Pituitary adenylate cyclase-activating polypeptide: Receptor?
VPAC receptor
Pro-opiomelanocortin: Source?
melanocytes, pituitary gland
Pro-opiomelanocortin: Receptor?
Melanocortin receptors
Substance P: Source?
sensory nerve fibers
Substance P: Receptor?
Tachykinin receptor
Vasoactive intestinal peptide: Source?
Sensory nerve fibers, Merkel cells
Vasoactive intestinal peptide: Receptor?
VPAC receptors
T/F: There are no lymphatics presesnt in fat lobules.
True
