KEY NOTES WK 3 Flashcards
atopic dermatitis comorbid with
allergic asthma and allergic rhinitis
sx of atopic dermatitis
pruritis (itch), eczematous dermatiits
facial and extensors in infants
flexural in older
Ig_ and atopic dermatitis
IgE
pathogensis of atopic dermatitis
skin barrier defects- filagrin genes
altered immune, cytokines, t cells
xerosis
filaggrin defieicny sx in atopic dermatitis
ichthyosis vulgaris, keratosis pilaris, and hyperlinear palms.
increases transepidermal water loss
Th_ in atopic dermatitis and Ig_
Th2, IgE, eosinophilia
also Th1
exogenous things that can worse atopic dermatitis
scratching, proteases from dust mites, staph aureus
genes in atopic dermatitis and what complex is it involved in
Filaggrin gene is found on chromosome 1q21 (minority of patents have FLG null mutation, its usually immune mediated reduction in epidermal differentiation)
which is involved in epidermal differentiation complex
acute vs chronic lesions of atopic dermatitis
acute: epidermal spongiosis (edema), T cell with CLA, mast cells, dendritic APCs (langerhans)
chronic: lichenified, hyperkeratosis, minimal spongiosis, more IgE langerhans, macrophages, fully granulated mast cells
what immune cell is absent in atopic dermatitis
neutrophils
2 key cytokines causing atopic dermatitis inflammation and causing a Th_
TSLP and IL-33 (Th2)
also IL22 IL17 IL4 and Il13
also Th1 cytokines INFy
IL5 for eosinophils
Chemokines: CTACK, CCR4, CCL17,
FUCK ETC…..
severity of atopic dermatitis correlates with
evels of thymus and activation-regulated cytokine (TARC)
which cytokines down regulate filaggrin expression in atopic dermatitis
TSLp, IL4, IL13
pruritis in atopic dermatitis because
allergen induced release of histamine
T cell cytokines: IL-31, stress induced neuropeptides (substance P and CGRP), proteases , eicosanoids (from arachidonic acid), eosinophil-derived proteins (major basic protein and eosinophil derived neurotoxin)
hypersensitivity rxn in allergic contact dermatitis
type IV (delayed)
steps of allergic contact dermatitis
sensitization (hapten binds skin and forms complex)
need subsequent exposure to get inflammatory response
gold standard test for allergic contact dermatitis
patch testing
examples of allergic contact dermatiis
nickle, cosmetics, gragnace, textiles, rubber gloves, glue
allergic contact dermatitis sx
pruritic, eczematous, edema, erythema, vesicle or papule then can be lichenification and scaling if chronic
geometric, linear or focal pattern
2 phases of allergic contact dermaitis
- sensitization phase: initial contact with allergen to develop immunologic memory, need sufficient exposure of sensitizing chemical
- elicitation phase; re-exposure triggers inflammatory rxn to minute quantities of allergen
how do haptens play a role in allergic contact dermatitis
hapten protein complex forms = antigen –> trigger immune response
keratinocytes release GM-CSF, TNFa, IL1, IL8, IL18 upon hapten exposure
langerhan and dendritic cells uptake antigen and express on HLA for T cells which get skin homing antigens
T cells become memory so then next exposure will react
elicitation phase of allergic contact dermatitis
Inducible Skin-Associated Lymphoid Tissue (iSALT)
effect T cell recruitment (APCs on langerhans and dermal dendritic cells)
irritant dermatitis differs from allergic contact dermatitis
ACD need complete avoidance
ACD need sensitization phase
irritant predisposes to ACD
treat irritant dermatitis
emollients
hardening= disappearance of sx
irritant dermatitis examples
wet to dry and heat cold, soaps, detergents, hand washing, cleaners, occupational, gloves
irritant dermatitis cause
physical damage to epidermis, temporally more immediate than ACD
damage keratinocytes
steps in irritant dermatitis
- epidermal insult (i.e. solvents removed lipids)
- danger signals (keratinocytes release alarmins- activate TLR, NF-kB)
- potential for allergic sensitization
seborrheic dermatitis sx
greasy, scaly patches and plaques on scalp, face, ears, intertrigous areas
cause of seborrheic dermatitis
malassezia (oleic acid, aryl hydrocarbon receptor), sebaceous glands from hormonal changes , cold and dry, immunocompromised (AIDs, Parkinson)
decreased by sun
Ig_ in seborrheic dermatitis
IgA and IgG
ifnalmamtory cytokines in seborrheic dermatitis
interleukin (IL)-1α, IL-1β, IL-4, IL-12, TNFα, and (IFN)- γ
malassezia species that cause seborrheic dermatitis
and what receptor they act as agonist for
Malassezia globosa and Malassezia restricta
aryl hydrocarbon receptor (AhR) –> Th17 cells –> inflame
aryl hydrocarbon receptor (AhR) from mallassezia activate what in seborrheic dermatitis
Differentiation of T-helper 17 cells.
hyperproliferation of epidermis in
serbohreic dermatitis and psoriasis
bacterial interference
resident microbes prevent colonization by pathogenic microbes via:
* (1) Competition for receptors or binding sites on host cells
* (2) Competition for resources like nutrients
*(3) Mutual inhibition by metabolic or toxic product release
urethra microbiom
urine not sterile
same as on perineum
vaginal microbiome change with age
after birth- lactobacilli
until puberty- cocci and bacilli
puberty- lactobacilli return and group B strep and clostridium, gardnerella…
menopasue- lactobacilli decrease
cervical mucous has
lysozymes (antibacterial)
if remove lactobacilli with antibitioccs can get
yeast colonization –> vaginitis
placenta and uterus
not sterile, good bacteria for pregnancies
bacterial vaginosis (dysbiosis) from increase in what species
gardnerella vaginalis and mycoplasma hominis
bacterial vaginitis sx
Vaginal malodor, increased white-gray discharge, possible dysuria and pruritus
complications of bacterial vaginosis
PID, pregnancy complications
chlamydia trachomatis has 2 morphologies
replicate body (replicative) and elementary body (infective)
different serotypes of chlaymdia
vs for chlaymida lymphogranuloma venereum
chlamydia- serotypes D-K
LV- serotypes L1-L3
transmission of chlamydia
sex, mucus, vaginal delivery
sx of chlamydia
female often asymptomatic
cervicitis, discharge…
complications of chlamydia
PID, neonatal conjunctivitis
reactive arthritis (cant see cant pee cant dance w me)
Chlamydia Trachomatis – Lymphogranuloma venereum (LGV)
genital ulcers –> lymphangitis and scars
Neisseria gonorrhea have what that virulence factors and which one makes have genetic variability
lipooligosacchardie
many plasmids for genetic variability
opa and pilin proteins for phase variation and prevent antibody binding and immunological memory
gonorrhoea phase variation via
opa and pilin proteins
gonorrhoea tramsision
sex, mucos, vaginal delitery
gonorrhoea sx
urethritis (women asymptomatic usually)
extra genital: pharyngitis, conjunctivitis, Gonococcal Dermatitis-Arthritis Syndrome
complications of gonorrhea
PID, infertile
Treponema Pallidum Pallidum - Syphilis
stages
1st stage: painless chancre (sore) into ulcer
2nd stage: ulcer disappears and get rash on palms and soles
latent stage
tertiary: granuloma, cardiac, and neurologic sx
congenital syphilis
impact baby bones, anemia, hepatosplenomgealy, brain….
Haemophilus ducreyi sx
- PAINFUL pustule that erodes into ulcer
mycoplasma genitalium and ureaplasma urealyticum
morphology
sx
no cell wall
urethritis, cervicitis (PID, infertile)
Trichomonas vaginalis sx
purulent yellow discharge with strawberry cervix, urethritis
STI comnplications
PID (chlamydia and gonorrhea esp.) (BV- flora changes)
Candida albicans virulence
dimorphic- yeast (spore) (at ph <6) or hyphae (at ph >7- more invasive)
biofilm formation
phenotypic switching, quorum sensing
Candida albicans sx
Vulvovaginal candidiasis: vulvar pruritus, burning, irritation, often without discharge or unusual odor
or cottage cheese
HPV (STI) causes
genital warts or genital cancer if high risk strain
HSV-2 is aka
genital herpes
HSV-2 sx
urethritis
congenital and perinatal infextion
latent in local sensory ganglia
HIV 3 key viral enzymes
protease, reverse transcriptase, and integrase
used to insert its DNA into host cell genome
transmission of HIV
sex, congenital, blood, trauma
ligands for transcyotis of HIV
GP120 ligand and GP41 co-ligand to attach to the galactosyl ceramide lipid on the new host’s epithelium
transmigration of HIV via
DC-SIGN
lymph node transmission of HIV
XR4 ligand and CXCR4 receptor on CD4+ T cells
or
R5 ligand and CCR5 receptor on macrophage
how does HIV get activated and replicate
activate if detects antigens or other STIs activate T cells and macrophage
replicate and release new virions (T cells die, macrophages survive)
***will stay latent in T cell until stimuli like a cytokine, inflame, APC, to become activated
where does HIV remain latent before activated and what cell does it affect and deplete the most
CD4+ T cells
stages of HIV
stage 1- lymphadenopathy
stage 2- latent CD4+ <500ul
stage 3- advanced
stage 4- AIDS (opportunistic infection), CD4+ <200c/u;l
how does HIV become AIDs
get AIDs if CD4+ cells are so depleted and then become more suscpecitible to getting another infection
HIV encephalopathy
invade CNS; i.e. dementia
which cancer is easy to screen for with Pap smear and HPV test
cervical cancer
central hypothalamic pituitary function causing disorders of reproductive tract
GnRH secretion
body fat, stress
causes amenorrhea
ovarian disorders and sx
I.e. PCOS, no viable follicles, dont respond to gonadotropins
hirsutism, infertility, anovulation, abnormal bleeds
common causes of uterine disorder/ endometrail dysfunction
homronal
fibroids (myomas) - tumor of mymoetrium
endometrial cancer
sx abnormal bleeds
pelvic infections from
gonorrhea, chlamydia, anaerobic bacteria
scarring can cause infertility
elevated WBC, fever
diagnostic approach to amenrrhea; 3 steps
- rule out pregnancy
- TSH (thyroid) and prolactin (pituitary)
- further tests based on history and physical exam
uterine disorders cause
i.e. damage stem cells that make endometrium (i.e. curettage, post part, chronic inflam) can cause amenorrhea and lining < 5mm
treat uterine disorders and make functional endometrium
progesterone and estrogen therapy
differentiate btwn endometrial vs endocrine causes of uterine disorders
endometrial: no withdrawal bleed after hormonal therapy
endocrine: withdrawal bleed (insufficient cyclic progesterone and estrogen stimulation)
primary vs secondary ovarian disoders
primary- premature ovarian insuffiecieny
secondary-lack of gonadotropin stimulation
premature ovarian insufficiency (lose ovarian follicles –> fail) from
genetics, metabolic, autoimmune, exogenous chmeicals
secondary ovarian insufficiency from
lack of gonadtopin stimulation from the brain –> low estrogen and progesterone prodcution
i.e. pituitary disorder or hypothalamic (stress, exercise)
primary ovarian insufficiency
< 40 yoa (follicular atresia) –> failure
primary ovarian insufficiency hormones
high FSH and LH (no feedback)
low estrogen (no follicles viable)
symptoms of primary ovarian insufficiency
(estrogen defincieny/menopasuse sx)
hot flashes, vaginal atrophy, decrease bone density
associated conditions with primary ovarian insufficiency
autoimmune polyglandular syndrome
diabetes, hypothyroid
genetics (FMR1, tuner, Y chromosome mocaism)
chronic anovulation sx and effects
follicles present, but dont mature and ovulate
amenorrhea w intermittent bleeds
increased estrogen exposure risks (without progesterone) (endometrial hyperplasia and carcinoma)
cause of chronic anovulation
thyroid
hyperprolactinemia (decreases GnRH)
PCOS
pituitary (Sheehan, trauma) and hypothalsmic
sheehan syndrome causing chronic anovulation
pituitary enlarges during pregnancy from lactotroph hyperplasia and then postpartum hemorrhage and hypotension and pituitary infarction
cant lactate postpartum (prolactin deficient)
amenorrhea (GnRH deficient)
fatigue, hypotesnion, hypoglycemia (lose ACTH, TSH)
hypothalamic amenorrhea homrones
low GnRH pulsattility –> decrease LH and FSH –> decrease progesterone and estrogen
rules out hyperprolactineamia and hypothyroidism (prolactin, TSH, free T4)
high prolactin suppresses
GnRH
hypothryoid cause anvoluation
high TRH stimulates prolactin –> suppress GnRH
treat hyperprolactineamia
dopamine agonist
cause amenorrhea
dysgenesis (abrnoaml uterus and vagina from genes)
imperforate hymen or transverse vaginal septum
endometrail adhesion, scarring from curettage, uterine tuberculosis (Asherman)
primary dysmenorrhea
menstural pain with no structural abnormalities
endometrial necrosis –> make prostaglandins –> myometrail contractions –> muscle hypoxia and pain fiber irritated
which substance causes pain in primary dysmenorrhea
prostaglandins from endometrial necrosis
endometriosis (endometrial tissue outside uterine lining) from
a) retrograde menstruation through Fallopian tubes into pelvic cavity, and/or
b) metaplasia of celomic mesenchyme into endometrial tissue, and/or
c) vascular or lymphatic dissemination of endometrial “seeds”
endometriosis inflammation triggers
cytokines and angiogenesis (new blood vessels with pain fibers)
scarring adhesions
pelvic inflammatory disease (PID)
infection of upper genital tract (i.e. STI)
can lead to scarring and adhesions if not managed
ovarian masses
non-neoplastic cyst
neoplastic
prolpase
and cause (which muscle)
many types but I,e uterus through pelvic floor or vaginal introitus (3 degrees ie.. 2nd degree is cervix through introits)
dysfunction of pelvic floor –> levator ani
esp if old and parous (given birth)
abnormal uterine bleeding causes
i.e. polyp, leiomyoga, adenomyosis, coagultpathy, ovculatory, malignancy, iatrogenic (IUD)
benign uterine masses (3)
endometrial polyps –>outgrowth of endometraila glands into lumen of uterus
adenomyosis –> endometrial gland in myometrium (downward growth)
leiomyoma (fibroids) - tumor in myometrium
adenomyosis vs endometrial polyp
EP= endometrial outgrowth into lumen of uterus
adeno= down growth of endometrial glands to myometrium
endometrial hyperplasia
what ratio
what hormone
increase gland: stroma ratio
from unopposed estrogen (I,e, chronic anovulation, peripheral androgens from obesity, estrogen therapy)
can progress to endometrial carcinoma
cervical dysplasia vs cervical cancer
Cervical dysplasia: Precancerous changes in cervical cells.
Cervical cancer: Malignant progression of dysplastic cells.
risks for cervical dysplasia and cancer
HPV (high risk 16, 18…)
tobacco
immunosuppression (HIV)
multiple sex partners
cervicitis from
changing vaginal microbiome - i.e. cyclic hormonal change pH and flora
with or without infection (Pap smear)
cervical atypia and dysplasia
what type of cell
causes
squamous cell
HPV (16, 18), smoking, sex, immunosuppress
HPV mechanism to cause cervical dysplasia
HPV hijacks epithelia cells to make viral particles and inactivates tumor suppressor genes
vaginitis and vulvitis from
changes in microbiomes (pH, hormones, exogenous trauma or pathogen)
infectious vs non infectious vaginitis
infectious: Bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis
non infectious: chemical, atrophic vagnitis, allergic vaginitis, foreign body
vulvo/vaginal malignancy
type of cell
squamous cell carcinoma
