Things that were highlighted in NAVDF notes Flashcards
What are the components of the extracellular lipid bilayer?
1) Ceramides
2) Free fatty acids
3) Cholesterol
In which layer of the epidermis are tight junctions found?
SG2 only!
Which layer of the epidermis provides a permeability barrier?
SG2, where tight junctions live
What cell is able to BYPASS tight junctions?
Langerhans cells – dendrites can pass, in order to sample superficial AGs
What is the rate limiting step for collagen synthesis
Prolyl hydroxylase
How does hyperbaric oxygen affect the dermis?
Promotes collagen formation (prolyl hydroxylase)
How does vitamin C affect the dermis?
Promotes collagen formation (prolyl hydroxylase)
What element is needed for lysyl hydroxylase oxidation?
Copper
What are the signals that induce anagen?
WNT, SHH, KGF, noggin (BMP antagonist)
What are the signals that inhibit anagen?
BMP
Signals that induce catagen
TGF-alpha
EGF
FGF-5
BMP
Signal that promotes hair shaft and IRS differentiation
BMP
(helps keep the epidermis between the follicles WNL)
How does noggin induce anagen?
Acts on Lef-1 transcription factor
Which species’ hair is nonmedullated?
Sphinx, sheep wool, angra goats
First hairs to develop
Sinus hairs
Location of tylotrich hairs on body
Scattered throughout, surrounded by neurovascular tissue
Which hairs have epitrichial sweat glands?
Primary only
Which section of hair follicle is shared in compound hairs?
Infundibulum
Which phase of the hair cycle is the bulb present in?
Anagen
Where does arrector pili muscle attach?
Bulge
Inner root sheath only present during this hair cycle phase
anagen and catagen
Which direction does IRS keratinize?
Outside in (henle first)
Mode of secretion of epitrichial sweat glands
MEROCRINE (not apocrine)
-Secretion via exocytosis
Which species do NOT have epitrichial sweat glands?
Rodents, ferrets
How are epitrichial sweat glands innervated?
NOT directly
Neural control via adrenergic agonists
Humoral control via adrenergic agonists
What medication can downregulate aquaporin 5?
Macrolides (horses treated for Rhodococcus)
What sweat gland change occurs in anhidrosis?
Downregulation of aquaporin 5 (water channel for rapid fluid movement)
Where are epitrichial sweat glands largest on the body?
Glaborous areas
Which part of hair follicle has the entrance for the epitrichial sweat gland?
Infundibulum
What cell surrounds equine sweat glands? #Unique
Myoepithelial cells (all animals), but in a loose basket-weave pattern with a rich surrounding blood supply!!
Gene responsible for midline white markings in horses
KIT mutation
Disease associated with midline white markings in horses
Piebaldism
Gene associated with Waardenburg type 2
MITF
Gene associated with white spotting and blue eyes +/- deafness in dogs
MITF
Mode of inheritance of waardenburg type 2 (White coat/blue eyes)
Autosomal dominant
Other name for waardenburg syndrome type 4 in horses
Lethal white foal syndrome
Gene in lethal white foal syndrome
Endothelin receptor type B (EDNRB)
Mode of inheritance of lethal white foal syndrome (EDNRB)
autosomal co-dominant
Clinical signs lethal white foal syndrome
White hair, blue eyes, deaf, aganglionic megacolon
What happens if a foal is homozygous for EDNRB mutation?
Lethal
(heterozygous for lethal white foal syndrome)
Gene for grey horse phenotype
Syntaxin 17 (STX17)
Mode of inheritance of STX17 in grey horses
autosomal dominant
What happens if melanin is outside of an endosome/unbound?
Cytotoxic
Gene in Gray collie syndrome
AP3 (adaptor protein complex 3)
Which bloodwork finding would you see in Gray Collie Syndrome
Cyclical neutropenia –> ultimately die
Silver cat with large cytoplasmic neutrophil granules and clumped melanin pigment on trichogram. Diagnosis?
Chediak Higashi syndrome
Gene mutation in Chediak Higashi syndrome
LYST/CHS1
Rate limiting step for melanin synthesis
Tyrosinase enzyme
Enzyme needed for eumelanin production
TYRP1, TYRP2, TYR
OCA type 4 in doberman pinschers –> clinical outcome
Make melanoma at a young age
Which gene in white doberman pinschsers makes them develop melanomas?
SLC45A2
Breed with SLC45A2 mutation, white coat, make melanomas
Doberman pinscher
Gene for OCA type 1
Tyrosinase
Gene for OCA type 2
TYRP1 (eumelanin)
Gene associated with cAD in Golden Retrievers
Filaggrin
RAB3C
Gene associated with cAD in GSD
Plakophilin 2
Gene enhancers associated with a risk haplotype
Gene associated with cAD in WHWT
Cytochrome P450 26B1
NAME THAT GENE
Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin
S100A8
Environmental influences that INCREASE cAD (5)
1) Urban
2) Regular bathing
3) C-section
4) Household hygeine
5) HDM exposure
Environmental influences that DECREASE cAD (4)
1) Rural
2) Multi-animal household
3) Non-commercial food
4) Skin barrier protective diet
Inflammatory signals released by keratinocytes (6)
1) ICAM-1
2) MHC class II
3) TARC
4) TNFalpha
5) IL-8
How does the microbiome affect the skin barrier? (3)
Healthy bacteria are associated with:
1) Increased ceramides
2) Decreased TEWL
3) Decreased SCORFAD
Mutation in cAD dogs across breeds, geography
TSLP receptor
Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT
TReg cells
What happens to the diversity of microorganisms on cAD skin?
Decreased diversity
Skewed to Staphylococcus
Biodiversity hypothesis
Modern version of hygiene hypothesis
Loss of macrodiversity in the environment and microdiversity within an individual leads to –>
1) Microbe dysbiosis
2) Immune dysfunction
3) Inflammatory dysresponse, lack of tolerance
4) Clinical symptoms of AD (also arthritis, diabetes, other immune mediated diseases)
How long does complete healing of the tympanic membrane take
21-35d
Thicker after injury
What is the origin of the outer membrane of the tympanic membrane (3-layer membrane)
Ectoderm–> outer ear origin
Center layer = fibrous
Inner layer = pharyngeal pouch origin
What happens to the sebaceous glands in OE canals
Less active
But MORE active/dilated ceruminous (apocrine) glands
What do Staphylococcus have to promote Type 2 inflammation?
Superantigens (endotoxin)
(Forces MHC cl II on APC and TCR on T cells to bind –> activate nonspecific, robust T cell response!)
Which 3 cell signals are implicated in hyperinnervation in cAD?
1) IL-31
2) NGF
3) Artemin (made when AHR is bound to pollutants)
How does allergen immunotherapy work? 4 major mechanisms
1) Desensitization of mast cells, basophils, eosinophils (QUICK): increase inhibitory Fc receptors, increase H2 receptors (block action of histamine)
2) Tolerance: generation of Treg, DCreg, IL10+ ILC (ILCreg), Breg, Tfreg; Reduction of Th2 to Th1 ratio
3) Decrease IgE, increase IgG1, IgG2, IgG4, IgA
4) Decreased # mast cells, basophils, eosinophils in tissue
What cells are involved in a Type 2 response
*Keratinocytes (alarmins, chemokines, IL-1)
*ILC2 (IL-5, IL-13)
*Th2 (IL-4, IL-13; express CTLA, CCR4, CRTH2)
*DC2 (OX40L)
*B cells (respond to IL-4 to make IgE)
*Eosinophils (express H4R, CRTH2 for prostaglandin binding)
What is FoxP3
Treg marker!
Transcription factor
Binds DNA to induce expression of Treg development and functional proteins
How does the Type 2 response affect the skin barrier?
1) Downregulates ceramide synthesis
2) Downregulates Filaggrin expression
3) Downregulates antimicrobial peptide expression
4) Alters skin protein and limit content
T or F: histamine is the most important molecule for induction of itch in atopic dermatitis
FALSE
NONhistaminergic pathway is more important (TSLP, IL4, IL13, IL31)
What type (greek letter) papillomavirus is BPV 1?
DELTA papilloma virus
This means not only does it infect keratinocytes, but ALSO dermal fibroblasts
4 major branches of the skin barrier
1) Physical (disorganized lamellar layers, reduction of CER 1, CER 9, CER; Lipids organized as hexagonal; decreased claudin/occludin of tight junctions, corneodesmosin)
2) Chemical (Decreased antimicrobial peptides; Natural hydration factors, lysozyme, phosphlipase A)
3) Immunological (Treg downregulated, Th2 increased. Hyperactive DC with extra IgE R. Keratinocyte alarmins, chemokines)
4) Microbiological (Dysbiosis; more Staphylococcus. Switch from M restricta to pachydermatis. Bacteria adhere to corneocytes more than normal)
What is the main physical blocker against penetration of external agents in the deeper epidermis?
Tight junctions in SG2
How do urocanic acid and carboxylic pyrrolidone (NMFs) affect skin pH and protease activity?
Decrease pH (more acidic)
Acidic pH INHIBITS protease activation
Outside-Inside-Outside theory
Primary defects in cutaneous barrier in AD → penetration of more allergens, stimulates immune system → exacerbation of skin barrier defect
***
T or F: there is a decrease in ceramides in NONlesional cAD skin?
True
Which TLRs induce production of TSLP by keratinocytes?
TLR3
TLR4
(NOT TLR2, TLR7)
4 phases of wound healing
1) Hemostasis/coagulation
2) Inflammation (neutrophils, then macs)
3) Repair/granulation phase
4) Remodeling/scar formation
What marks the END of the coagulation phase
Fibrin clot
Cells that stores TGF B
Platelets
What type of collagen is present in scar tissue
Collagen 1
What type of collagen is present in granulation tissue
Collagen 3
Which growth factor is overexpressed in proud flesh. Which cell is hyperplastic in proud flesh?
TGF-B1
Mast cell hyperplasia
Which medications are synergistic with HBOT (4)
1) Fluoroquinolones
2) Aminoglycosides
3) Beta-lactams
4) Amphotericin B
Which phase of wound healing would you expect to see exudate (septic or nonseptic)
Inflammatory phase
(neutrophils getting eaten up by macs)
Risk factors for poor wound healing (6)
1) Infection
2) Medications
3) Comorbidities (age, endocrine, liver/kidney, neoplasia, immune-med)
4) Nutrition (need Glu, protein, Mg, Vit A)
5) Location
6) Radiation tx
What is ENDEMIC pemphigus foliaceus?
*Fogo salvagem (Brazil)
*Sand fly salivary antigen LJM11
Also: young, poor women in S Tunisia. High temp, UV radiation, contact with ruminants, infections, genetic susceptibility
What drugs can cause PF in cats?
*Cimetidine
*Doxycycline
*Econazole/Neomycin/Triamcinolone/Amoxicillin
*Itraconazole/lime sulfur
Major autoantigen for canine PF
DSC-1
T or F: Absence of anti-DSC IgG can be used to rule out PF
FALSE.
Many dogs with trunk-dominant PF do not have detectable anti-DSC IgG, even though their major autoantigen is still DSC-1
Feline PF treatments
*Oral glucocorticoids
*Pulse therapy not helpful in cats
*Apoquel (1 mg/kg BID tapered to 0.5mg/kg BID)
+/-
*Cyclosporine
*Chlorambucil
Which layer of haired skin/foot pad has the most DSC1
Stratum granulosum, Stratum spinosum
How does autoantigen IgG lead to blisters in AISBDs?
Fab region binds to autoantigen, which induces C1q component of complement system –> Complement-dependent cytotoxicity –> Blisters
Mechanism of steric hinderance –> acantholysis
Binding of auto-Ab prevents bonding of desmoglein on same cell AND desmosomes between 2 cells
Mechanism of signal transduction –> acantholysis
Auto-Ab affects the signal transduction pathway is affected. Leading to steric hinderance and desmoglein depletion
*Overexpression of c-myc in PV dogs interferes with signaling cascade needed for DSG-3 expression
Autoantigen for BP
*BP180 (Collagen 17)
>
*BP230 (BPAG1e)
Autoantigen for EBA
Type VII collagen
What factors are released by inflammatory cells that lead to blister formation in AISBDs?
*Neutrophil elastase
*MMP-9
*ROS
Degradation of BMZ structures –> results in deep blister
Which AISBD is mucosal/MC dominant with minimal skin lesions
MMP
Which AISBD is haired skin only
BP
Generic modified cyclosporine achieved ______ blood concentrations at 1 hr post-administration than Atopica
HIGHER (but only for the 1st hour!!)
After 1.5 hours, no significant difference!!!
We need bioequivalent pharmacokinetic studies based on AUC + Cmax
Mechanism of cyclosporine
1) CsA binds cyclophillin
2) Cyclophillin binds to calcineurin, which inhibits calcineurin function (does not dephosphorylate NFAT)
3) NFAT cannot translocate to nucleus
4) No increase in IL-2
Which disease was successfully treated with mycophenolate monotherapy
ECLE
Higher doses of Apoquel can cause immunosuppression via reduction in _________
*IL-2
*IL-15
*IL-18
*IFNg
*Induces apoptosis of CD4+, CD8+ T cells
Which cells are NOT affected by Bruton’s tyrosine kinase
T cells
BCR not present in T cells!
Histopath difference between SGPS and sarcoidosis in dogs
*No neutrophils in sarcoidosis
*Sarcoidosis does not affect adnexa or extend to panniculus
Histopath difference between reactive histiocytosis and sarcoidosis in dogs
Reactive histiocytosis is bottom heavy
Sarcoidosis is top heavy
Which special stain can help determine CAEDE vs Sweets-like?
Luna stain (eosinophilic infiltration amount)
Which MMPs are upregulated in Perianal fistula
MMP 9, MMP 13
*Implicates macrophages in pathogenesis
*Explains extensive tissue destruction
Feline plasma cell pododermatitis: Sex
Males (esp neutered)
What is the virulence factor and target in Exudative Epidermitis?
*Exfoliatin toxin
*DSG-1
Histopath Darier Disease
*Suprabasilar acantholysis
*Corps ronds/ round bodies = dyskeratotic keratinocytes
*Basal cell vacuolation
*Decreased lateral desmosome adhesion
*Separation of keratin filaments from desmosomes –> Circular accumulation of keratin around nucleus, “perinuclear keratin rings”
Which level of epidermis are corps ronds present in Darier Disease
Stratum spinosum
Parakeratotic stratum corneum: “grains”
Trichophyton proteases that may cause proteolytic acantholysis
*Substilisins
*Fungalysin metalloproteases
*Di-peptyl-peptidases
*Amino- or caroboxy- peptidases
Target of Exudative epidermitis
DSG1
Cutaneous and Renal Glomerular Vasculopathy (AKA “alabama rot”: clinical signs
Acute, with rapid deterioration
Edema, erythema –> hemorrhage, ulcers
HINDlimbs, footpads, mucosae
25% get acute kidney injury AKI. Usually AKI happens AFTER skin lesions.
Breeds with familial vasculitis (all in puppies)
1) Beagles (familial necrotizing arteritis). ANCA positive.
2) GSD Familial Cutaneous Vasculopathy. Autosomal recessive. 2’ vaccination? Foot pads, nasal bridge. Self recover, but relapse with future vax.
3) Jack Russel Terrier Familial Cutaneous Vasculopathy. Vaccination? Ulcers, alopecia on boney prominences, pinnae, footpads.
4) Scottish Terrier Hereditary Vasculitis (pyogranuloma and vasculitis of the nasal planum); Autosomal dominant. Ulcer of nasal planum.
5) Shar Pei Vasculitis (life threatening! Idiopathic. Fever, hemorrhagic papules, deep ulcers, epidermal detachment. Tx GC)
Familial dermatomyositis: environmental factors
*Estrus
*Sun exposure
*Trauma
*?? virus, vaccine, drugs, toxins, stress
Familial dermatomyositis: genes
Risk alleles:
*PAN2
*MAP3K7CL polymorphisms
*MHC cl II haplotypes
Hyperkeratotic Erythema multiforme: sex
Males > females
Which cytokine is important for EM, by upregulating MHC cl I and clI, enabling keratinocytes to present MORE antigens?
IFNg
Triggers for Erythema multiforme in cats
*Infections: FHV
*Drugs (up to 100%): usually antimicrobials
*Neoplasia (thymoma)
*Idiopathic
What causes thickening of the BMZ in DLE, MCLE, hyperkeratotic EM
Deposition of immunglobulins and immune complexes
Which chemokines are UPREGULATED in FAS lesional skin in cats (2)
TARC/CCL17
RANTES/CCL5
ASIT response in feline asthma; glucocorticoid impact
*Not completely allergen specific
*Response is REDUCED by concurrent systemic steroids
*Response is UNAFFECTED by inhaled steroids
Horse breed with high rate of Culicoides hypersensitivity
Icelandic born horses
Which cytokine is upregulated in skin of IBH horses
TSLP, IL-13
NOT IL-4
Which type of T cell is higher in skin from IBH horses
CD4»_space;> CD8
Which transcription factor is downregulated in skin of IBH horses (lesional and nonlesional skin)
FoxP3 (TF for TRegs)
T or F: Blood eosinophil numbers correlate with IBH severity
TRUE
Function of 5-hydroxytryptamine (5-HT) at high and low doses
Low dose: itch
High dose: pain
Most effective treatment for IBH
Insect avoidance
-move away from standing water
-stable horses at night
-use fans
Horse breeds predispoed to Atopic Dermatitis
*Arabians
*Finn horses
*Thoroughbreds
Atopic Dermatitis in horses: top 3 clinical signs
1) Urticaria
2) Pruritus
3) Urticaria + Pruritus
Location of pruritus for Atopic Dermatitis in horses
Face, trunk, flexural surfaces
+/- urticaria
Reasons why prednisolone > prednisone in horses
*Poor absorption
*Rapid excretion
*Failure of hepatic conversion of prednisone to prednisolone via 11-B hydroxysteroid dehydrogenase
Reason glucocorticoids may trigger laminitis
*Vasoconstriction
*Increased circulating insulin or glucose
*Decreased collagen production in lamellae
*Diminished keratin production in hoof wall
*Diminished growth of coronary band
MOA of pentoxifylline
*Synthetic xanthine derivative
*Inhibits phosphodiesterase
ALLERGY: inhibits T and B cell activation, increase IL-10, PGE2, decrease leukocyte adhesion, decrease neutrophil superoxide, degranulation, IFNg, NK cell activity
*Rheological effects
*Improves wound healing (Increased fibroblast collagenases, decrease TNFa)
Efficacy of ASIT in horses
70% improve
2/3 stay in remission after ASIT d/c
Which medications should NOT be combined with azathioprine, as it inhibits xanthine oxidase
Allopurinol, ACEi (enalapril)
Allopurinol is a xanthine oxidase inhibitor, so more of the azathioprine is pushed to active metabolite form (XO would make inactive metabolite = safer)
Which medication should NOT be combined with azathioprine, as it inhibits TPMT
Sulfasalazine
Myelosuppression
Why are IVIg beneficial for autoimmune diseases
IVIg increases catabolism of pathogenic IgG
IVIg preferentially binds to neonatal Fc receptors (FcRn). If bound to FcRn, Ig is protected from degredation. Because IVIg is taking all the FcRn spots, pathogenic IgG cannot bind–> so it is degraded.
4 anti-inflammatory mechanisms of doxycycline
1) Decrease cytokines (IL-1, IL-6, IL-8, TNFa)
2) Inhibit MMPs
3) Reduce leukocyte chemotaxis
4) Reduces NO synthase function
MOA of niacinamide
Endogenous inhibitor of PARP-1
1) Inhibits proinflammatory cytokines
2) Reduces ICAM-1 expression (decreased neutrophil chemotaxis)
3) Reduces B cell differentiation
Which medication should be avoided with colchicine
Cyclosporine
Both are p-glycoprotein substrates!
T or F: expression of antimicrobial resistance genes is a virulence factor
FALSE.
Not necessarily more invasive or proinflammatory
May need to trade a virulence factor in order to have a resistance mechanism (fitness cost)
2 virulence factors to help Staphylococcus evade the host immune response
*Coagulase (coa gene)– promotes fibrin clot scaffold for tissue invasion –> abscessation, protection of bacterial clusters from neutrophils
*von Willebrand factor-binding protein– known as an indicator of pathogenic potential
What are the 2 major clonal lineages of MRSP?
ST 71 (Europe, Japan)
ST 68 (USA)
Same mecA gene as MRSA. Probably came from the same CoNS.
Risk factors for MRSA in horses
*Hospitalization
*Preventative penicillin use
*Ceftiofur
*Aminoglycosides
*Exposure to previously colonized horses
*Antibiotics within 30 days
*Admission to neonatal ICU, hospital
What bacteria are considered normal commensals in most food animals
S aureus
S hyicus
What is the MRSA sequence type that is present in food animals and humans (+ dogs, rats, horses)
ST 398
What is the infectious stage of Dermatophilus congolensis
Ovoid Zoospores!!
Bacteria that can cause:
-Necrotizing Fasciitis and Myositis
-Toxic Shock Syndrome
Streptococcus canis!
-M Protein: antiphagocytic, destroys C3 convertase
Which antibiotic can TRIGGER Toxic Shock Syndrome
Fluoroquinolones.
Can trigger more expression of superantigen TSST-1 by S. canis!
What’s special about Listeria monocytogenase
Facultative intracellular gram + rod in MACROPHAGES
Escapes humoral immune response
Which cytokines are crucial for inducing macrophage anti-leishmanial activity
IFN-g
IL-2
TNFa
(Th1)
Immune response type that makes you RESISTANT to Leishmania infection
Th1
Immune response type that makes you SUSCEPTIBLE to Leishmania infection
Th2
Histopath stain to find Leishmania amastigotes
Giemsa stain
Predisposed signalment for Nocardia infection
Male, immunocompromised
Fungi that are present on NORMAL dog and cat skin
*Alternaria
*Aspergillus
*Cladosporium
*Penicillium
*Rhizopus
*Trichoderma
Infective portion of dermatophyte
Arthrospore
Forms by segmentation and fragmentation of fungal hyphae
Predisposed breeds for M canis
*Yorkshire terrier
*Pekingese
*Persian
*Himalayan
In what phase of the hair cycle does dermatophyte growth cease?
Telogen, as no new keratin production
-Hairs are weak and easily broken
What is the dermatophyte antigen that is MOST immunologically active?
What type of hypersensitivity reaction does it produce?
Glycopeptide (cell wall)
-Carb portion: immediate-type hypersensitivity
-Peptide portion: delayed-type hypersensitivity
Which dermatophyte species is least likely to cause alopecia
Microsporum persicolor
Infects surface keratin, does NOT invade hair
Scaling w/no alopecia
What dermascopy findings would you expect with dermatophytosis vs alopecia areata
Dermatophyte: comma hair
Alopecia areata: Exclamation point hair
T or F: Malassezia pachydermatis can grown on a media without lipids
FALSE. Lacks fatty acid synthase gene (like all Malassezia)
Uses lipid fractions from within peptones of Sabouraud’s dextrose agar
But technically called “non-lipid-dependent”, because it is the only Malssezia that can grow on Sabouraud’s dextrose agar
PAMPs identify _____ on Malassezia
*Mannan
*Zymosan
PRRs for Malassezia
C-type lectins! Need Ca2+ to bind carbohydrates
*Langerin
-Recognizes mannose, beta-glucans
-on Langerhan cells
Many fungi
*Mincle
-Recognizes glucosyl and mannosyl-glycolipids
-on Phagocytes
Malassezia specific
*D-lectin + Mincle stimulate proinflam cytokines (IL-10, TNFa, MIP2)
Antimicrobial resistance in Malassezia (2)
1) Increased expression of ERG11 gene
Encodes lanosterol 14-alpha-demethylase (Azole target)
2) Increased expression of Drug efflux pumps (CDR1, CDR2; MDR1)
Black grain mycetomas organisms
*Curvularia geniculata
*Madurella
White grain mycetomas organisms
*Acremonium
*Pseudallescheria
At what temperature are dimorphic fungi a yeast? At what temperature are dimorphic fungi a hyphae/mold
Yeast in TISSUE
Hyphae at ENVIRONMENTAL temperatures
ie: Sporothrix, Histoplasma, Blastomyces, Coccidiodes
Why is Pythium not a true fungus
1) NO CHITIN in cell walls
-Instead: cellulose, B-glucan
2) NO ERGOSTEROL in cell membrane
3) Sexual process = oogamy
4) Infective biflagellate zoopspores in wet environments
Characteristics of mycetomas (3)
1) Tumefaction (swelling)
2) Draining tracts
3) Grains (aggregates of fungi)
T or F: Pythium can be visualized on histopath with PAS
FALSE. Lack chitin
T or F: Oomycosis is zoonotic
FALSE. Infective zoospores only form in water, not in tissue
Immune response needed to clear Blastomycosis
T-cell mediated
Directed to BAD-1 (adhesin)
Diagnosis of Blastomycosis
Urine ELISA is best! Can use to monitor response to treatment
Serology: 41-90% sensitive, 90-100% specific
Predisposed dogs to Coccidiodes immitis
*Young, male dogs.
*Boxers, Dobermans
+/- immunocompromised (more severely affected)
Best stain to visualize Coccidiodes immitis spherules
Pap stain
(capsular wall = refractile, purple-black. Cytoplasm= yellow. Endospores = red-brown)
Can also use PAS, Wrights stain
What needs to be added to DTM for Trichophyton verrucosum
Thiamine (100%), inositol (80%)
What needs to be added to DTM for Tricophyton equinum
Niacin
T or F: Orf (Parapoxvirus) is zoonotic
True
(Also, Pseudopox in cows causes Milkers Nodules. Orf looks similar. Depends on if contact is sheep vs cow!)
Which type of immune response can be detrimental to clearance of BOTH pythium and Leishmania
Th2
3 Oncogenes for Papillomavirus (and how they affect the immune system)
E5:
-Downregulate MHC cl I (immune evasion)
-Decreased gap junctions (KC separate from neighbors)
-Interacts with PDGF (more mitosis)
E6:
-Downregulate p53 (which usually holds cell cycle in G1-S)
E7:
-Cell transformation, pRb phosphorylation
Cat breeds with more Malassezia dermatitis
Devon Rex
Sphynx
Most common Malassezia sp in cat ears
Malassezia nana
Most common Malassezia species on the cat overall
Malassezia pachydermatis
Most common Malassezia sp in cat ears
Malassezia nana
What stimulates phospholipase activity in Malassezia pachydermatis?
Endogenous opiod peptides
Beta-endorphins in skin of dogs with dermatitis
Higher phospholipase activity in OE/dermatitis dogs
What culture media do you use for most Malassezia species
modified Dixons agar (lipid enriched)
1) contact plates = convenient
2) Detergent scrub sampling = gold standard but research only
T or F: Cats with FIV/FeLV are at increased risk for dermatophytosis
FALSE. They are NOT at increased risk
3 main stages of dermatophyte infection
1) Arthrospores adhere strongly to keratin
-Mediated by adhesins on arthroconidia, proteases like subtilisins
-Within 2-6 hours of exposure
2) Conidial germination (germ tube emerges from arthroconidia, penetrates SC)
3) Invasion of cornified tissues by producing proteolytic enzymes (keratinase, elastase, collagenase)
Mechanical injury and humidity facilitate penetration
*Hyphae form arthroconidia within 7 days –> complete lifecycle
MOA of chlorhexidine
Biguanide compound
Affects cell membranes at low concentrations
Congeals cytoplasm at high concentrations
MOA of itraconazole
Inhibits fungal cytochrome P450 enzyme (140alpha demethylase)
Prevents conversion of lanosterol to ergosterol
Ergosterol needed for cell wall integrity, activity
What happens if you combine ketoconazole with ivermectin, midazolam in dogs
or
Cyclosporine in dogs, cats
INCREASED plasma concentrations
(Cytochrome p450 inhibitors)
What is different about fluconazole compared to the other azoles
*Water soluble, minimally protein bound
-Others are lipophilic
*NOT affected by concurrent antacids, do not need food for absorption
*Poor efficacy against dermatophytes
Which antifungal medication has the LOWEST MIC for Microsporum and Trichophyton
Terbinafine!
What is the unique feature of FHV1 on histopath
Necrosis of sweat glands
Prominent eosinophils
Which flies feed at daytime?
*Stable fly (Stomoxys)
*Horse fly (Tabanus)
*Horn fly (Haematobia irritans)
What disease is this? Vector?
Habronemiasis
“Summer sores”
Vector: Stable fly, Stomoxys
Cow Ventral abdomen
Stephanofilaria stilesi
Filaria
Vector: Haematobia irritans
“Horn fly”
Cow dorsum
Warbles
“Cow grubs”
*Hypoderma bovis (spinal cord migration)
*Hypoderma lineatum (esophageal migration
*Cows»_space; Horses
*Warbles = L3 larvae
*Tx = avermectins
What disease is this? Which fly is a vector for this disease
Onchocerca cervicalis
Culicoides, Simulium (Black fly)
Which flies are responsible for these lesions? What disease is this?
Equine aural plaques
Caused by equine papillomavirus
Vectors: 1) Black fly, Simulium
2) Stable fly, Stomoxys
Breeds predisposed to generalized demodicosis
*American Staffordshire terrier
*Staffordshire bull terrier
*Chinese Shar Pei
*French bulldog
Where in the skin does Demodex gatoi live
Stratum corneum (like sarcoptes)
NOT hair follicle
Which dogs are predisposed to amitraz toxicity
Small breeds: Pomeranians, Chihuahuas
CHIHUAHUAS ARE ON THE LABEL
Reversal to amitraz toxicity
Yohimbine, atipamezole
Which breeds are sensitive to ivermectin? Mutation?
Collies
Australian shepherd dogs
Shetland sheepdogs
English sheepdogs
ABCB1 gene (formerly mdr1); autosomal recessive–> nonfunctional P-glucoprotein = ATP-dependent transmembrane transporter protein, esp at the blood-brain barrier. Cannot transport drugs OUT of the CNS
What medications should be avoided with ivermectin
Other substrates of P-glycoprotein efflux transporter
ALSO Spinosad products —> inhibitor of P-gp!
Which nonpeptidergic c-fiber is most important for cAD itch
NP3
Inflammatory itch
Neuromediators: IL-31, IL-4/IL-13, Serotonin, Histamine, LTC4
What are the nerve elongation factors
TNFa, IL-31, NGF
These are all increased in cAD skin
What are the 4 receptors that are sensitized by G protein coupled receptors to transmit itch up the nerve
Ca2+ channels:
TRPV1 (vanilloid)
TRPA1 (Ankyrin)
Na+ voltage gated channels:
Na v1.7
Na v1.9
What histamine receptors are present on sensory neurons
H1, H4 = ACTIVATING
H3 = INHIBITING
Which breeds develop Acral Mutilation Syndrome
- German Shorthaired pointers
- English pointers
- English Springer spaniels
- French spaniels
What induces complete remission in 100% of cats with idiopathic ulcerative dermatitis on their necks
Environmental enrichment
“Behavioral ulcerative dermatitis”
Which topical flea prevention should NOT be used on rabbits
Fipronil
DO NOT USE ON RABBITS OR HEDGEHOGS
Which medication should NOT be combined with ivermectin
Spinosad (Comfortis)
Spinosad acts as a p-glycoprotein inhibitor. Increased ivermectin in CNS –> toxicity
Which 2 dermatophytes are in the stratum corneum ONLY (not in hair follicles)
1) Trichophyton mentagraphytes
2) Microsporum persicolor
Would you find a honeycomb liver on AUS of a dog with glucogonoma-derived hepatocutaneous syndrome
NO. But you would see a pancreatic mass (or metastatic liver nodules)
HONEY COMB LIVER IS ABSENT IN GLUCAGONOMA HCS
How is most T3 made in the body
Peripheral tissue deiodinization of T4 (from I4 to I3)
What is the best test for hypothyroid diagnosis
fT4 + TSH
TSH increases the specificity of fT4
How long prior to thyroid testing should glucocorticoids be discontinued
At least 4 weeks
Effect of Sulfonamides on thyroid
*TT4, fT4, T3: Low
*TSH: High
TRUE HYPOTHYROIDISM –> reversible
TMS will decrease follicle function
Increase in TSH because no negative feedback from fT4
What results of endogenous ACTH test would you expect with a pituitary tumor derived AHC
+ ACTH if pituitary origin
-ACTH if adrenal origin (negative feedback)
Expected findings on ACTH stim of a dog with PDH
Look at 8hr first. If ABOVE 40nmol/L: consistent with HAC.
Then we need to know if PDH or uncertain origin:
PDH confirmed if:
* 4-hr: <40 nmol/L (in normal range)
* 8-hr: >40 nmol/L BUT >50% reduction from baseline
How does TMS affect thyroid levels
Inhibits thyroid peroxidase (which adds iodine to tyrosine). Results in true, reversible hypothyroidism
Low TT4, fT4
High TSH
May result in a goiter
How does euthyroid sick syndrome affect thyroid levels
1) Inhibits 5’/3’ deiodinase, which converts T4 to T3 in the peripheral tissue
2) Decreased TSH secretion
3) Decreased thyroid protein binding
Low TT4, fT4
Normal to low TSH
Treatment for cutaneous plasmacytosis (only dogs get this! Like MM)
Chemotherapy: Melphalan!
What is a risk factor for BISC, especially on haired, pigmented skin in cats?
FcaPV2
Treatment for perianal gland adenoma
Neuter resolves perianal gland adenoma in 95% of cases
Gene, mode of inheritance for Dermoid Cysts
FGF 3, 4, 19
Autosomal recessive
Dorsal midline
Which virus is associated with SCC in cats, horses
FcaPV2 (cats)
EcPV2 (horses)
Which ceramides contain linoleic acid
Ceramides 1, 4, 9
Papilloma oncogene that binds pRb (TSP)
E7
IHC markers for histiocytoma
CD1a, CD11c/CD18, E-cadherin, IBA-1
E-cadherin are specific for histiocytoma
How can you tell if a mass is cutaneous reactive histiocytosis vs histiocytoma
Histiocytoma (LC): Top heavy, E-cadherin +
Cutaneous reactive histiocytosis (DC): Bottom heavy, E-cadherin -
MOA of selegiline hydrochloride
IRREVERSIBLE inhibitor of monoamine oxidase (MAO)
-Increase in dopamine
-Downregulate ACTH secretion
-Best in dogs with pars intermedia tumor
DOES NOT WORK FOR HAC. But owners like it bc selegiline is metabolized to amphetamine –> increased alertness
Why do cats need to ingest arachidonic acid
No delta-6-desaturase
Which parasiticide is TOXIC TO BIRDS
Imidacloprid (Advantage)
Which parasiticide should NOT be given to finches
Ivermectin
Which parasiticide should NOT be given to chelonians (turtles)
Ivermectin
Treatment for mites and lice in guinea pigs
Ivermectin SQ ONLY!!!
PO has poor GI absorption in guinea pigs
Which species develops cutaneous lymphoma most commonly
Hamsters
Why are rabbit abscesses more inspisated than dogs/cats
Rabbit heterophils are myeloperoxidase- deficient
Which hormones ARE elevated in Ferret Cushings?
- Androgens (andostenedione, 17-alphahydroxyprogesterone, DHEAS)
- Estradiol
Cortisol NOT elevated
Which receptor is present on ferret adrenal tissue in both health and HAC animals
LH receptors
Activation of pre-existing LH receptor proteins with HAC!
*Confirmed with GnRH stimulation test
GnRH tells pituitary to release LH –> binds to LH receptors on adrenal glands –> Adrenal glands make estradiol, androgens
Life-threatening sequela of ferret adrenocortical disease
Cystic urogenital anomalies –> URINARY BLOCKAGE
Prostatic most common (but also in females)
Stranguria, dysuria
Medical treatment of adrenocortical disease in ferrets
Deslorelin acetate (Suprelorelin) implant
GnRH analog: downregulates GnRH receptors in pituitary gland –> inhibits LH, FSH production
AFTER an initial stimulation (esp in males)
Which cytokines are elevated in culicoides hypersensitivity
IL-4
IL-5
IL-13
IL-31
Th1 is unaffected or decreased. Th1 is PROTECTIVE against CH
3 risk factors for sarcoids
1) Exposure to BPV (but also in healthy skin!)
2) Local cutaneous trauma (allows viral activation)
3) Genetic predilection (certain MHC profiles, QH, Ap, Arabian, TB, WB)
Which virus is commonly found in ocular and genital SCC in horses
EcPV-2
(in 100% in one study!)
Necessary but not sufficient to induce SCC
Which goat parasite can cause pruritus due to nerve pain
Parelaphostrongylus tenius
Neuro exam, CSF
Tx: Fenbendazole
Causative agent of herpes mammillitis in cows
BHV-2
Direct contact, insect vectors
