Pathology Exam Iv

Front 1

Normal Mammalian Sexual Development

Back 1

1. Establishment of chromosomal sex
2. Development of Gonadal sex
3. Development of Phenotypic sex

Front 2

Abnormalities of Phenotypic Sex

Back 2

-Pseudohermaphrodites
-persistent mullerian duct syndrome
-androgen insensitivity
-steroid 5-a-reductase deficiency
-Adrenogenital syndrome

Front 3

Pseudohermaphrodites

Back 3

-Chromosomal constitution and gonadal sex match but Internal or external genitalia are ambiguous
-Gonads of one gender and ducts of opposite gender
-Male pseudohermaphrodites are more common than female pseudohermaphrodites
-Most mechanisms are not understood

Front 4

Persistent Paramesonephric Duct Syndrome
Mullerian Remnant Syndrome

Back 4

-Abnormality of Phenotypic sex
-XY genotype, SRY+
-Testes are present with female internal tubular genitalia
-Receptor abnormality, lack of Mullerian Inhibiting Substance or Anti-mullerian hormone receptor
-Inherited autosomal recessive trait
-Homozygous dogs with descended tests are usually fertile and will transmit trait to all offspring
--produces carriers or affected dogs
-Occurs in miniature schnauzers
-Dx is confirmed by presence of 78,XY chromosome constitution, bilateral testes, and present of all mullerian duct derivatives

Front 5

Persistent Paramesonephric Duct Syndrome
Clinical Abnormalities

Back 5

-Undescended testes attached to uterine horns
-Vas deferens are located in the wall of the uterus
-Bilateral oviducts, complete uterus with cervix, and cranial portion of a vagina
-Bilateral scrotal testes, unilateral or bilateral cryptorchidism may be present also
-Dogs may present with pyometra, UTI, prostate infection, or Sertoli cell tumor

Front 6

Androgen Insensitivity

Back 6

-Testicular feminization or Male feminization
-Reported in dogs, mice, rats, cats, cattle, horses
-Mutation in the X-linked androgen receptor gene
-Deficiency or abnormality of the cytosol receptors for androgen
-Testosterone production is normal, conversion to dihydrotestosterone is normal, but target organs are unable to respond to hormones
--complete or partial failure of androgen-dependent masculinization
--Degree of Dysfunction depends on whether the androgen receptor is non-functional or partially functional
-Paramesonephric/Wolffian system does not develop or does not fully develop
-No male external genetalia, internal male genetalia
-Uterus, cervix, and vagina regress, normal response to mullerian inhibitory ssubstance

Front 7

Non-functional androgen receptor

Back 7

-Androgen-dependent masculinization is absent
-Complete diagnosis for androgen insensitivity and testicular feminization
-Affected males present as females that are sterile and do not cycle
-Mullerian duct derivatives are absent (like normal male)
--regression is not dependent on androgens
-Occurs in DSH cats

Front 8

Steroid 5-alpha reductase deficiency

Back 8

-Abnormality of phenotypic sex
-Absence of changes that occur under influence of dihydrotestosterone
-No closure of the urethra and scrotum
-Will have development of the

Front 9

Genital Abnormalities

Back 9

-Sex abnormalities
--phenotypic, gonadal, chromosomal
-Ovarian Abnormalities
--developmental, inflammatory, neoplastic
-Uterine Tube Abnormalities
-Uterus Abnormalities
--non-inflammatory or inflammatory

Front 10

Phenotypic Abnormalities of Sex organs

Back 10

-Pseudohermaphrodites
-True hermaphrodites
-Chimeras
-Have to do histologic assessment to determine if male or female gonadal tissue is present

Front 11

Clinical Indicators of DSD

Back 11

-Lack of estrus
-Enlarged or masculinized clitoris
-increased anus-vulva distance

Front 12

Examples of Pseudohermaphroditism

Back 12

-Mullerian remnant Syndrome
--XY chromosomes, SRY+
-Androgen insensitivity
--XY chromosomes, SRY+
--receptor issue
-XY, SRY-
--gonadal dysgenesis
--results in hypoplastic or undifferentiated gonads
--Female genotype

Front 13

Androgen Insensitivity in Horses

Back 13

-Vagina is a blind sac
-No tubular internal genitalia
-Seminiferous tubules are lined by inactive sertoli cells
-No male accessory sex glands
-Normal appearing mammary glands

Front 14

XX disorders of Sexual Development

Back 14

-Most are SRY negative
-Often have ovotestes (true hermaphrodites)
-Ambiguous or female phenotype
-Autosomal recessive in American cocker spaniels
-Associated with the polled gene in goats

Front 15

True Hermaphrodites

Back 15

-Both male and female gonadal tissue is present
-Chromosomal make-up is a chimera
--mosaic
--XX with or without SRY gene
-Often penis is not fully masculinized
-One or both testes may palpable, or not, but are undescended
-Dx confirmed via karyotype and histopathology

Front 16

Unilateral Hermaphrodite

Back 16

-Ovotestis on one side

Front 17

Bilateral hermaphrodite

Back 17

-Ovotestis on both sides

Front 18

lateral hermaphrodite

Back 18

-Ovary on one side and testis on other side
-Ducts are abnormal

Front 19

Causes of True Hermaphroditism

Back 19

-Congenital adrenal gland hyperplasia
-Fetal exposure to sex hormones
-Testicular feminization syndrome
-XY gonadal dysgenesis
-XY gonadal agenesis
-Chromosomal abnormalities

Front 20

True Hermaphrodite affected breeds

Back 20

-American and English cocker spaniel dogs
-Polled goats
-German shorthaired pointer
-Weimaraner
-Beagle
-Kerry Blue terrier
-Chinese pug
-West Highland white terrier
-Basset hound
-Doberman pinscher
-Pomerania
-Viszla
-Walker

Front 21

XX/XY Chimeras

Back 21

-Two or more types of cells, each with different chromosomal constitution
-Different cells arise from a different source
-Product is a hermaphrodite
-Free martin

Front 22

XX-XY Mosaics

Back 22

-2 or more types of cells
-Cells arise from the same individual
-Non-disjunction at mitosis in a single zygote

Front 23

XO, XXX, XXY

Back 23

-Chromosomal abnormalities
-Cause gonadal hypoplasia without phenotypic ambiguity

Front 24

DAX1 gene

Back 24

-Member of the nuclear hormone receptor
-Superfamily whose expression is mainly restricted to steroidogenic tissues
-Expressed in adrenal glands, ovaries, testes, hypothalamus, and pituitary gland
-Interruption of expression may be cause of hypogonadotropic hypogonadism (HH)

Front 25

SOX9 gene

Back 25

-Regulates SRY expression
-Encodes a transcription factor involved in chondrogenesis and testis development

Front 26

Bovine Freemartin

Back 26

-Chimeras
-Affects female in a set of male/female twins
-Anastomosis of vasculature allows male hematopoietic cells to colonize the female fetus
--venous anastomoses between umbilical cords
--anastomosis is normal
-Both are chimeras, but male is minimally affected
-Mullerian inhibiting substance is produced by the male testes, affects female development

Front 27

Female Bovine Freemartin

Back 27

-Small gonads with no germ cells or partially converted to testes
-Externally appears female
--vestibule and vulva are hypoplastic
--clitoris is enlarged
-May be comprised of seminiferous-like tubules
-Mullerian duct will be normal or cord-like structure that does not communicate with the vagina
-Seminiferous vesicles are present
-Other wolffian structures are present

Front 28

Freemartin Pathogenesis

Back 28

-Normal Vascular anastomosis in twin fetuses leads to exchange of blood between fetuses
-Female is exposed to cells and hormones produced by the male testes
-Female is masculinized
-Male produces testis-determining factor (SRY product)
--ovarian inhibition

Front 29

Features of Freemartin Calves

Back 29

-Hypoplastic uterine horns
-Paired hypoplastic vesicular glands
-Short, non-patent vagina
-Ovotestes are partially surrounded by epidodymal tissue
-Clitoris is enlarged
-Hypoplastic vulva and vestibule
-Prominent tuft of hair ventral to vulva
-Male twin is minimally affected
-Both twins are chimeras in hematopoietic cells

Front 30

Ovarian Developmental Abnomalies

Back 30

-Agenesis: complete absence of the ovary and its associated primordium
-Hypoplasia: incomplete development or underdevelopment of the ovary
--will have decreased number of cells
--may or may not have abnormal chromonsomes (XO, XXX)
--follicles are usually absent

Front 31

Cystic Graafian Follicle

Back 31

-Prolonged interval between parturition and 1st post-partum estrus
-Occurs in cows and pigs
-Larger than normal follicles that persist for more than 10 days without CL formation
-Failure of egg release from follicle
-AKA cystic ovarian degeneration in cows
-Suspected due to deficient LH

Front 32

Anovulatory Luteinized cysts

Back 32

-Develop from follicular cysts with delayed or insufficient release of LH
-Can be considered part of Cystic Ovarian Degeneration
-Can be associated with nymphomania

Front 33

Cystic Corpus Luteum

Back 33

-Center of cyst fails to fully luteinize, get cystic center
-Usually incidental finding
-No interference with length of estrus cycle

Front 34

Oophoritis

Back 34

-Inflammation of the ovary
-Rare
-Can be viral cuase or bacterial cause
-Systemic diseases that affect the reproductive tract

Front 35

Turner Syndrome

Back 35

-Partial or complete absence of 1 X chromosome (XO)
-Hypogonadism, small fibrotic ovary
-Individual will be short with a broad-based neck, narrow aorta
-Not an inherited problem

Front 36

Follicular Atresia

Back 36

-Excessive atresia can result in infertility
-Selective loss of ovarian follicles via atresia occurs through apoptosis
-Most obvious in granulosa cell layer

Front 37

Dysgerminoma

Back 37

-Rare germ cell neoplasm
-Analogous to seminoma in males
-Relatively benign
-Pale brown appearance of parenchyma with a central collagenous scar

Front 38

Teratoma

Back 38

-Rare, benign tumor
-Usually well-differentiated
-occurs in 2 of the 3 embryonic germ layers
--epithelium
--fibrous tissue
--endothelial tissue
-Composed of non-proliferating somatic tissues, jumble of well-differentiated cells

Front 39

Granulosa Cell Tumor

Back 39

-Most common ovarian neoplasm in large animals
-Solid, cystic, polycystic morphologies
-Can produce testosterone in mares
--results in stallion-like behavior
-Anestrous, continuous estrous, or intermittent estrous are all possible
-Will have atrophy of the contralateral ovary due to inhibin production and decreased FSH
-Can occur in pregnant mares
-Can have thecal differentiation, results in granulosa-theca cell tunor

Front 40

Ovarian Epithelium

Back 40

-Can resemble endometrium
-Contiguous with mesothelium

Front 41

Cystadenoma

Back 41

-Ovarian epithelial tumor
-Common in dogs, rare with spaying
-May be lined by epithelium that is serous or mucinous
-Mucinous tumors are filled with sticky mucin, tend to be multiloculated
-Can be bilateral

Front 42

Hydrosalpinx

Back 42

-Distention of the uterine tube by clear fluid
-Can be due to blockage of outflow of normal tissues
-Will lead to salpingitis, inflammation of the uterine tube

Front 43

Salpingitis

Back 43

-Inflammation of the uterine tube and oviducts
-Due to bacterial and viral infections

Front 44

Pyosalpinx

Back 44

-Accumulation of purulent fluid in the lumen of the oviduct
-Pus in the fallopian tubes
-Can be accompanied by an obstruction

Front 45

Non-inflammatory conditions of the uterus

Back 45

1. Developmental abnormalities
2. Endometrial hyperplasia
3. Positional abnormalities
4. Subinvolution
5. Endometrial atrophy
6. Adenomyosis
7. Endometriosis

Front 46

Segmental Aplasia of the Uterus

Back 46

-Failure of the Mullerian ducts to reach the urogenital sinus
-Normal on one side and missing on the other side
-Prostaglandin produced in the blind uterine horn can cause CL lysis in the contralateral ovary during pregnancy
-Long-term distension can cause inability to produce endometrial prostaglandin
--no regression of CL
--Compression Atrophy leads to damage

Front 47

Endometrial Hyperplasia

Back 47

-Increase in the size and number of endometrial glands with no increase in stroma
-Due to increase in estrogen (large animals) or progesterone (dogs and cats)
-Simple endometrial hyperplasia can lead to cystic endometrial hyperplasia, which can cause endometritis and pyometra

Front 48

Endometrial Hyperplasia in Cattle

Back 48

-Due to excessive and prolonged estrogen stimulation
-May have granulosa cell tumor or ovarian follicular cysts
-May be due to ingestion of estrogenic cpds

Front 49

Endometrial Hyperplasia in Dogs

Back 49

-Receptors for estrogen on endometrial cells are stimulated, results in synthesis of intracellular receptors for progesterone
-Progesterone converts endometrium to secretory mode
-Associated with long-acting progestational cpds used to delay estrus

Front 50

Uterine Torsion

Back 50

-Positional abnormality
-Results in compression of venous outflow
-Causes hypoxia, infarction, and shock
-Predisposing factors include pyometra, mucometra, and pregnancy
-Just because calf is alive does not mean cow is OK

Front 51

Uterine Prolapse

Back 51

-Uterine horn with pregnancy and uterine body
-Urinary bladder and intestines may be involved
-Results in hypoxia, infarction, and shock in cow
-Occurs in cows, ewes, sows
-May result in uterine artery rupture
--bleeds into broad ligament and can bleed out
-Usually occurs after birth or late in pregnancy
-Predisposing factors include dystocia, hypocalcemia, and estrogenic plant ingestion

Front 52

Uterine Subinvolution

Back 52

-Delayed and abnormal involution of the zonal placental sites
-Mostly in dogs
-Can have reproductive consequences
-Placental sites are thicker than normal, rough, brown, and composed of hematoma and cell debris
-Collagen deposition occurs deeper, along with dilated glands
-Trophoblast can invade myometrium wither perforation
-Hyperplastic endometrium with congestion

Front 53

Endometrial Atrophy

Back 53

-Due to Loss of Ovarian function
-Occurs in seasonal anestrus animals
-Older animals that are no longer cycling can also have endometrial atrophy

Front 54

Hematuria

Back 54

-Occurs in rabbits due to uterine issue
-Endometrial venous aneurisms
-Uterine adenocarcinoma
-Uterine polyps
-Urinary bladder polyp
-Pyelonephritis
-renal infarcts

Front 55

Endometriosis

Back 55

-Heterotrophic endometrial gland with neoplasia-like behavior
-Occurs mostly in primates

Front 56

Endometritis

Back 56

-Inflammation of the endometrium
-related to introduction of semen, pregnancy, parturition, and post-partum involution
-most infections start in the endometrium
-Progesterone makes the uterus susceptible to infection
-Estrogens increase WBC phagocytosis and induice cervix opening
--Protects against infection and allows drainage (also exposure)
-Prostaglandins facor uterine motility
-Can destroy epithelium and decrease reproduction
-Truperella pyrogenes

Front 57

Endometritis Pathogenesis

Back 57

Chronic endometritis → decrease in capability to produce prostaglandin → CL persists and progesterone production persists

Front 58

Pyometra

Back 58

-Acute or chronic suppurative inflammation of the uterus
-Pus accumulates within the uterine lumen
-Endometrial hyperplasia can lead to pyometra
-Bone marry atrophy and immuno-complex glomerulonephritis in dogs can cause also

Front 59

Twin Placenta

Back 59

-Non-infectious lesion
-Twinnig in the mare and cow are pathological, NOT normal!
-Chorion not in contact with the endometrium does not develop villi
-Splits available blood flow
-Decreased area for nutrient exchange

Front 60

Adventitial Placentation

Back 60

-Non-infectious lesion
-Compensatory measure in the ruminant
-Response to inadequate number of placentomes

Front 61

Hydroallantois

Back 61

-Non-infectious lesion
-Excessive acccumulation of fetal urine within the allantoic cavity
-Can cause abortion, uterine paresis, or retention of the placenta

Front 62

Hydranmnios

Back 62

-Non-infectious lesion of placenta
-Increased fluid in the amnion
-Associated with fetal abnormalities, especially facial abnormalities

Front 63

Umbilical cord abnormalities

Back 63

-Excessive length leads to torsion
-Frequent finding in aborted equine fetuses
-Hemorrhage and edema must be present to confirm
-Thromobosis and mineralization of placental blood vessels secondary to ischemia are histologically detectable
--important for diagnosis

Front 64

Congenital Goiter

Back 64

-Occurs in sheep and goats
-Can cause dystocia
-Due to deficiency in diet of the dam

Front 65

Placentitis

Back 65

-Chorionitis
-Amnionitis
-Allantoitis
-Allantochorionitis

Front 66

Descending placentitis

Back 66

-Hematogenic
-From somewhere else, systemic infection
-Ex: Leptospira
-Usually bacterial or viral infections

Front 67

Ascending placentitis

Back 67

-Infection ascending from the cervix
--Can be due to chorionic cervical star
-Most commonly bacteria and fungi (especially in mares)

Front 68

Large animal abortion

Back 68

-Abortion → release of prostaglandins → regression of corpus luteum → decreased progesterone
-No progesterone, pregnancy is not maintained
-Dead fetus is expelled

Front 69

Carnivore and swine abortion
Multiparous abortion

Back 69

-DEath of the fetus is NOT followed by CL regression
-Dead fetus is retained until normal time of parturition

Front 70

Pathology of Infectious Abortion Mechanisms

Back 70

1. Fetal hypoxia and stress → fetal corticosteroid release, prostaglandin release → CL regression
2. Uterine contractions → fetal expulsion
3. Microorganism infection of fetus → fetal septicemia/parasitemia→ fetal death in-utero

Can have expulsion of fetus with no sequelae, or can have endometritis
-retention of fetus with mummification can lead to severe endometritis

Front 71

Mummification

Back 71

-Possible outcome of fetal death
-Fetus will be small, dessicated, and diffusely red
-Conceptus is retained in the uterus and progressively dehydrates
-Enzyme producing bacteria have to be absent and uterus has to be closed
-Sometimes associated with viral infections

Front 72

Maceration

Back 72

-Bacterial contamination of the fetus
-Endometritis and pyometra are likely to occur
-Fetus rots
-Introduction of bacteria leads to lytic enzymes and decomposition

Front 73

Abortion with fetus and placenta not involved

Back 73

-Different/external cause for abortion
-Damage limited to the uterus can trigger abortion
-May occur with equine arteritis virus
--causes vasculitis and necrosis of the endometrium and myometrium
--fetal hypoxia results
-fetus can be viable at the time of expulsion

Front 74

Stillbirth

Back 74

-Delivery of a dead fetus at a stage when it should have been viable

Front 75

Pathogenesis of Infectious Abortion

Back 75

1. Descending or ascending infection of the chorionic trophoblast
2. Cell necrosis is induced by direct or indirect cytopathic effect
3. Cellular release of inflammatory mediators, prostaglandin included
-causes edema and inflammation
4. Hypoxia is triggered by thickening and effacement of trophoblast, endothelial cell necrosis and thrombosis
5. Fetal hypoxia and stress causes corticosteroid release and prostaglandin release
6. uterine contraction and fetal expulsion
7.If organisms are able to infect the fetus, fetal septicemia occurs

Front 76

Herpesvirus

Back 76

-Causes necrosis
-have intranuclear inclusion bodies
-Cause mid to late term abortions
-Can cause neonatal death

Front 77

Equine Herpesvirus 1 and 4

Back 77

-Respiratory disease, vasculitis, encephalomyelopathy
-Causes necrosis of the lung, liver, and lymphoid organs
-All have intranuclear inclusion bodies
-Losses for equine industry
-EHV-1 causes respiratory disease, fatal vasculitis, and myelopathy secondary to vasculitis
--can affect camelids
-Fetal liver will have faint white spots and multifocal areas of necrosis
-Will see inclusion bodies on histology

Front 78

Bovine HerpesVirus

Back 78

-Infectious Bovine Rhinotracheitis
-Infectious bovine pustular vulvovaginits
-causes inflammation of the penis, sheath, vulva, and vagina
-Pathogenesis and lesions are similar to EHV-1
--multifocal necrosis
-Fetus is autolysed, usually 5-8 months gestation

Front 79

Bacterial abortion vs. Viral abortion

Back 79

-Bacterial: rotten fetus
-Viral: increases birth defects and early embryonic loss
-Gestational age at time of infection is important for pestiviruses

Front 80

Suid Herpesvirus 1

Back 80

-Pseudorabies, Aujesky disease
-SMEDI
-Distribution and lesions are similar to EHV-1
-Abortion, neonatal mortality
-Multifocal white spots on liver
-Encephalitis can occur, especially in species eating raw pork

Front 81

Canine Herpesvirus 1

Back 81

-Multifocal visceral necrosis with renal hemorrhages
-Cause of neonatal mortality and presumptive cause of abortion
-Direct viral cytopathic effect on parenchymal cells and endothelium

Front 82

Pestiviruses

Back 82

-Bovine Viral Diarrhea
-Border disease
-Hog Cholera

Front 83

Bovine Viral Diarrhea

Back 83

-Bovine Pestivirus
-Causes early embryonic death/abortion
-Fetuses will be small for gestational age, will have defects
-May cause mummification, stillbirth
-Weak calves
-Able to infect ant cell type

Front 84

Bovine Viral Diarrhea effects on Pregnancy by gestation date

Back 84

1. BVD infection 0-60 days: death of conceptus, embryo is usually resorbed
2. 60-120 days: fetal growth retardation, ocular and nervous system malformations, abortion
3. after 6th month: possible abortion
4. non-cytopathic BVD in 2nd-4th month: immunological tolerance for disease may occur
--results in persistently infected animal and constant shedder

Front 85

Hog Cholera

Back 85

-Pestivirus
-Foreign animal disease
-Similar to BVD
-Tonsils best for diagnosis
-Causes abortions
-Big meaty spleen with necrosis

Front 86

Hairy Shaker Syndrome

Back 86

-Ovine Pestivirus/Border Disease
-Similar to BVD

Front 87

Arterivirus

Back 87

-Equine Viral Arteritis
-Causes vasculitis of the endometrium
--can lead to fetal hypoxia and stress, cortisol release
-Fetus rarely has lesions, dies due to secondary lack of O2 from endometrium
-Stallions act as carriers

Front 88

Porcine reproductive and Respiratory Syndrome Arterivirus
PRRS

Back 88

-Similar to Equine arterivirus
-Causes secondary bacterial infections
-Hypofertility, abortion, pneumonia, and infant death
-Lesions: chorionitis, vasculitis, pneumonia
-Virus replicates within macrophages and endothelium

Front 89

Streptococci, E.coli, and Pseudomonas as cause of equine abortion

Back 89

-Cause ascending placentitis, leading to thickened chorionic cervical star
-Aborted tissues are filled with agents and are INFECTIOUS!

Front 90

Fungi and equine abortion

Back 90

-Cause ascending placentitis, leading to thickened chorionic cervical star

Front 91

Leptospira interrogans and abortions

Back 91

-Multifocal chorionitis
-Fetal nephritis and pneumonia
-Placenta is thickened, edematous, necrotic, or can be totally normal
-Have to run PCR for diagnosis

Front 92

Mare Reproductive Loss Syndrome

Back 92

-Eastern tent caterpillar

Front 93

Ascending infection in uterus

Back 93

-Causes cervical star lesions

Front 94

Hematogenous infection in uterus

Back 94

-Multifocal chorionic lesions

Front 95

Herpesvirus and Abortions

Back 95

-Multifocal necrosis in numerous organs

Front 96

Bluetongue and abortions

Back 96

-Orbivirus
-Causes erosions and ulcers in upper GI
-Results in stillbirth, mummification, early embryonic death, infertility
-Causes defects and growth retardation
-Microvascular injury
--before day 70: abortion of absorbtion
--70-130: hydranencephaly and death
--after day 200: Ab production and fetus is virus-free at birth
-Has been migrating northwards
-DO NOT export!!!

Front 97

Truperella Pyrogenes and Bovine Abortion

Back 97

-Causes endometritis, placentitis, and fetal pneumonia
-Intraleisional coccobacilli
-Often fatal for adults and young
-Usually not an outbreak situation
-Will have huge colonies of bacteria in the lung
-Hemorrhagic tracheal casts in the lung

Front 98

Brucella, Campylobacter, and Chlamydophila and Bovine Abortion

Back 98

-Yellow/brown to gray exudate
-fetal lymphadenitis, vasculitis, abomasitis, bronchopneumonia
-Intercotyledonary
-Bacteria are morphologically different, but outcome is similar

Front 99

Coxiella burnetti

Back 99

-Q-fever
-Resistant bacterial agent
-Causes chorionitis and fetal septicemia
-Cotyledons and intercotyledonar chorionic areas are covered by whitish, chalky, exudate
-Thickened and leathery placenta
-Suppurative placentitis
-Occurs in US and Europe
-Can also occur in Humans!

Front 100

Bovine Mycotic Abortion

Back 100

-Aspergillus
-Zygomycetes
-Cotyledons are eroded away, covered in fibrin-like material
--fungal plaques

Front 101

Bacterial Abortion in Bovine

Back 101

-Rotten fetus
-Cotyledons with or without intercotyledonary spaces
-Lungs and abomasal contents are important for culture

Front 102

Viral Abortion in Bovine

Back 102

-INcreased birth defects and early embryonic loss
-gestational age at the time of infection is important for pestiviruses

Front 103

Bluetongue in Sheep and Goats

Back 103

-before day 50: absorption and abortion
-Day 50-80: necrotizing encephalopathy
-Last trimester: immunocompetence

Front 104

Porcine Parvovirus

Back 104

-Causes stillbirth, mummification, early embryonic death, infertility, reduced litter size
-Infects rapidly dividing cells

Front 105

Causes of Porcine Abortion

Back 105

-Pestivirus
--hog cholera
-African Swine Fever Virus
-Porcine circovirus 2

Front 106

Canine herpesvirus 1 and abortions

Back 106

-Multifocal visceral necrosis with renal hemorrhages
-causes neonatal mortality in dogs

Front 107

Feline Herpesvirus and abortion

Back 107

-Rare cause of neonatal mortality
-presumptive cause of abortion
-Multifocal visceral necrosis
-Often causes conjunctivitis, rhinitis, and tracheitis

Front 108

Brucella canis

Back 108

-Causes abortions after day 50
-Can be a source of brucellosis for other species
-Will have gray/green vaginal discharge
-Epididymis or testicular degeneration

Front 109

Bacteria, Fungi, and Protozoa affecting multiple species

Back 109

-Chlamydophila:
--ruminants, pigs
-Listeria Monocytogenes:
--sheep, cattle, primates
-Leptospira interrogans: all species
-Brucella:
--ruminants, dogs
-Salmonella:
--horses, cows, sheep
-E. coli:
--all

Front 110

Listeria Monocytogenes

Back 110

-Affects ruminants and primates
-Associated with rotting vegetation
-Multifocal necrotizing and suppurative chorionitis and fetal septicemia
-Coccobacilli are visible with histochemical and immunohistochemical stains
-Causes abortions, neonatal deaths, encephalitis
-Only affects the brainstem in sheep and cattle

Front 111

Cysts in the Vulva and Vagina

Back 111

-Arise from Gartner ducts (Wolffian remnants) or from vestibular glands of Bartolinus
-Hyperestrogenism or inflammation can predispose formation
-Need to remove the entire cyst for it not to come back

Front 112

Vulvo-vaginitis

Back 112

-Viral, bacterial, mycotic, traumatic, or chemical damage
-infectious pustular vulvovaginitis due to BHV1 or BHV4
-Can be due to multi-systemic illness
--Taylorella equigenitalis

Front 113

Vulvular Edema

Back 113

-In pigs
-Zearalenone toxicity
-Estrogenic
-Can cause reproductive issues

Front 114

Neoplasia of the Vulva and Vagina

Back 114

-Leiomyoma
--most common in dogs
-Squamous cell carcinoma
--due to UV radiation and papillomavirus
-Fibropapilloma
--most common tumor in cow vulva
-Transmissible Venereal Tumor
--not common in US

Front 115

Scrotal dermatitis

Back 115

-Trauma predisposed to increase in size due to testicular neoplasms
-Skin diseases

Front 116

Developmental Abnormalities of the Testes

Back 116

1. Cryptorchidism
2. Hypoplasia
3. Degeneration

Front 117

Cryptorchidism

Back 117

-Incomplete descent of the testis
-Often genetic condition, sex-limited autosomal recessive
-Most common genital disorder in male cat and horse
-Can be unilateral of bilateral, unilateral is more common
-May be due gubernaculum testis lack of development, improper position, excessive growth, failure to regress
-After puberty retained testis becomes small and fibrotic
-Histologically testicle is hypoplastic and degenerate

Front 118

Cryptorchidism predisposing factors

Back 118

-testicular hypoplasia
-Estrogen exposure during pregnancy
-Breech labor, interfering with blood supply to the testes
-Delayed closing of the umbilicus, causes delayed ability to increase abdominal pressire

Front 119

Cryptorchidism sequelae

Back 119

-Reduced fertility
-predisposition to developing tumors, remove undescended testicle!

Front 120

Causes of testicular hypoplasia

Back 120

-Cryptorchidism
-Intersex development
-Poor nutrition
-Gonadotropin deficiency
-Specific genes
-Endocrine or cytogenetic abnormality
-Ketoconazole, ethanol, acetaldehyde, cannabinoids

Front 121

Testicular degeneration

Back 121

-Testicle was normal and shrank
-Common
-Multiple causes and mechanisms
-Targets are sertoli cells, germ cells, or interstitial cells
--usually all 3 are affected
-More mature stages of spermatogenesis are preferentially affected

Front 122

Orchitis

Back 122

-Inflammation of the testicle
-Intratubular
-Necrotizing
-Granulomatous
-Can have ectopic germplasms after rupture of tubules
--act like foreign bodies
--Immune privileged sites, germ cells can cause foreign body rxn
-Process can spread to epididymis and tunnica vaginalis
-Fistula rarely develops through scrotum

Front 123

Testicular Neoplasia

Back 123

-Germ cell tumors:
--seminoma
--teratoma
-Gonadal stromal tumors
--Sertoli cell tumor
--interstitial cell tumor/leydig cell tumor

Front 124

Seminoma

Back 124

-Germ cell tumor
-From primitive seminiferous epithelium
-Does not produce significant levels of hormones
-Multicentric origin within the testes
-Locally invasive without metastasis
--Metastasis is possible in horse and humans
-Soft and bulging when cut, has fine fibrous trabeculae

Front 125

Sertoli Cell Tumor

Back 125

-gonadal stromal tumor
-Firm, white mass with fibrous tissue dividing it into lobules
-Locally invasive and may metastasize
-Spindle cells organized in tubules and/or sheets
-BIG tumor, occludes normal tissue
-Usually local, but can metastasize
-Produce estrogen, have feminizing effect
--also causes bone marrow toxicity and other effects

Front 126

Sertoli Cell Tumor and Estrogen

Back 126

-1/3 of all sertoli cell tumors produce estrogen
-Bone marrow toxicity
--non-regenerative anemia
--granulocytopenia
--thrombocytopeina
-Liver damage can occur
-Hypothyroidism and alopecia
-Hyperplasia or squamous metaplasia of prostate acini
-Will have atrophy of testicles/penis
-Reduced libido

Front 127

Interstitial Cell Tumor
Leydig Cell Tumor

Back 127

-Tan/orange
-Most common testicular tumor in dogs
-Non-invasive, finely encapsulated
-Generally not hormonally active
--if androgens are produced, usually does not cause hyperandrogenism
-Histologically looks like round/polyhedral/spindle shaped cells
--have vacuolated cytoplasm

Front 128

Spermatic granuloma

Back 128

-Sperm escapes from normal containment
--acts as foreign body
-Can be due to trauma or influx of urine along the vas deferens
-Can occur due to infections (Brucella)

Front 129

Prostatitis

Back 129

-Inflammation of the prostate
-Usually ascending, organisms invade via prostatic urethra
-Most often gram- bacteria
-Can be due to trauma

Front 130

Porstate Hyperplasia

Back 130

-Common in old dogs and old humans
-Hypertrophy with enlargement
-Altered androgen:estrogen ratio
-Castration is preventative and therapeutic
-Acinar hyperplasia can be due to androgenic effects or other steroids
-Fibromuscular hyperoplasia may be caused by estrogen excess

Front 131

Prostate Squamous Metaplasia

Back 131

-Squamous metaplasia of the acinar prostatic epithelium
-Adds to estrogen-induced hypertrophy of the prostate
-Often due to presence of sertoli cell tumor

Front 132

Prostatic adenocarcinoma

Back 132

-most common prostatic neoplasm
-Most common in old dogs
-Derived from prostatic glandular epithelium of alveoli and ducts
-Very aggressive neoplasm
--70-80% of cases metastasize at time of diagnosis

Front 133

Transmissible Venereal Tumor
TVT

Back 133

-Transmissible neoplasm
-On the genitalia of both sexes of dogs
-Mesenchymal, round/oval cells
-May spontaneously regress
-Transmissible neoplasm!
-Genetically distinct from host

Front 134

Squamous cell carcinoma on Penis

Back 134

-Mostly in dogs and horses
-Proliferative and ulcerative lesion
-Exophytic, ulcerative mass
-Can be locally invasive and hard to excise
-Can look like sarcoids on horses, Biopsy!!

Front 135

Embryology of the mammary Glands

Back 135

-Appear as 2 linear thickenings or ridges
--"milk lines"
-Detectable on the ventrolateral ectoderm of the dog embryo at day 25 of gestation
-Supported by specialized mesoderm
-Extend from axillary to inguinal region
-Overlying epithelial cells and underlying mesenchymal cells
-Development occurs due to communication between ectodermal/epithelial cells and mesenchymal cells

Front 136

Development of the mammary gland

Back 136

-Ectodermal cells migrate along the mammary lines, coalesce into placodes
-Each placode gives rise to a single gland
-Ectodermal cells of the placode proliferate to form solid cords (mammary buds)
-Mammary buds sprout into the underlying mesoderm as a branching structure
-Number of sprouts determines the number of papillary duct orifices that will develop on each nipple sheath

Front 137

Nipple Sheath

Back 137

-Area of specialized epithelium
-Forms the raised teat in adults
-Evagination
-Each teat usually has several duct orifices
-Each duct branches into a lobe of the adult gland
--acts as an individual functional unit
-Number of teats depends of species, number of teat orifices depends on species

Front 138

Duct orifices per teat

Back 138

Dog: 7-16, can get up to 22
Cat: 4-7
Ruminant: 1

Front 139

Mammary glands per species

Back 139

-Goat and sheep: 2 teats
-Mare: 4 glands, 2 teats
-Cow: 4 glands, 4 teats
-Sow: 8-18 glands and teats
-Primates: 2 glands, 2 teats

More teats allows for more developing embryos

Front 140

Dog mammary glands

Back 140

-Usually develop 5 pairs of glands
-2 thoracic
-2 abdominal
-1 inguinal

Different glands will metastasize to different regional lymph nodes

Front 141

Cat mammary glands

Back 141

-4 pairs of glands
-Axillary pair
-Thoracic pair
-Abdominal pair
-Inguinal pair
-At birth, only large ducts have developed (teat is not fully developed)
--only extend a short distance into the underlying mesenchymal tissue from the teat
-With puberty, release of estrogens from ovary induces cell proliferation at the terminal ends of the ducts
-Release of estrogen stimulates formation of ductal system

Front 142

Terminal End Buds

Back 142

-Terminal ends of the large ducts in a cat
-Induced by estrogen at puberty to develop and grow
-Site of stem cell proliferation
-Form alveolar system and secretory gland

Front 143

Estrogen and mammary duct proliferation

Back 143

-Stimualtes proliferation of the ducts at the onset of puberty

Front 144

Progesterone and mammary ducts

Back 144

-Increased progesterone induces formation of lobules and alveoli
-Levels increase in diestrus and pregnancy
-Allows for formation of milk secretory unit (alveoli)

Front 145

Prolactin and mammary ducts

Back 145

-Pre-secretory alveolar cells differentiate into secretory alveolar cells
-Increase in the size and number of secretory alveolar cells

Front 146

Mammary gland at parturition

Back 146

-Secretory ductal-lobular-alveolar structure

Front 147

Duct development "clock"

Back 147

1. Pre-pubertal or 1st pro-estrus: small duct
2. Pro-estrus: early ductules, early lobules
3. Oestrus: some intralobular loose stroma
4. Early diestrus: more intralobular loose stroma
5. Late diestrus: Ductal branching, alveolus formation
6. Early anestrus: alveolar regression, regressive features present in alveoli
7. Late anestrus: all inactive lobules and regressive features

Front 148

Normal Histology of the mammary gland

Back 148

-Multiple papillary ducts open to teat surface
-Teat ducts are lined by stratified squamous epithelium
--surrounded by a highly protective circular smooth muscle sphincter
-Longitudinal and transverse smooth muscle fibers and elastin within the dermis of the teat and along larger ductal system
--Smooth muscle constricts when milk is present, release when milk needs to be let down
-Sebaceous glands empty onto the skin NOT into hair follicle
-Gradual transition of cells

Front 149

Mammary tree of life

Back 149

Secretory unit → ductal units → reservoir → environment

Front 150

Histology of Teats

Back 150

-Each teat duct opens into the teat sinus
--teat sinus is lined by bilayered cublidal to columnar epithelium
--flattened myoepithelial cells on outside
-Interlobular ducts empty into the teat sinus
--have bilayered cublidal epithelium with peripheral myoepithelial cells
-Smaller interlobular ducts are lined by monolayer of cublidal epithelial cells
--fewer peripheral fusiform myoepithelial cells
--allows for "peristalsis" of the duct

Front 151

Ductal growth

Back 151

-Elongation and branching occur due to epithelial cell proliferation
-Penetrate through the gaps between myoepithelial cells
-Occurs with estrogen and progesterone stimulation

Front 152

Mammary alveoli

Back 152

-Functional unit of the Mammary gland
-Lined by a single layer of epithelial cells and externally star-shaped myoepithelial cells
-Seretory phase epithelium is cuboidal to columnar with intracytoplasmic lipid droplets
--fat in milk
-Epithelial and myoepithelial cells reside on and produce basement membrane
--mostly collagen IV, laminins, and heparin sulfate proteoglycans

Front 153

Myoepithelial cells in normal mammary tissue

Back 153

-Stellate, NOT fusiform

Front 154

Mammary stroma

Back 154

-Supports epithelial structures
-Derived from specialized mesoderm
-Subdivided into intralobular stroma and interlobular stroma
-INTRAlobular stroma: loosely arranged and finer collagen bundles
-INTERlobular stroma: Separates lobules, formed by thicker and more tightly organized collagen bundles

Front 155

Mastitis

Back 155

-Infection of the mammary gland
-Economically important disease
--Causes severe economic loss, esp. in cows
-Less common in ovine and caprine
-Rare in other species
-Most cases are caused by bacteria

Front 156

Bacteria causing mastitis

Back 156

1. Staphylococcus agalactia, staphylococcus aureus, mycoplasma
-Mammary gland serves as the reservoir
-Persistent infection
2. E. coli
-Environmental reservoir, infection from environment
-SEVERE inflammatory response
3. Streptococcus uberis, streptococcus dysgalactia
-Mammary gland or environment is the reserovir
-Organisms can persist in mammary gland OR environment

Front 157

Mastitis infection

Back 157

-Usual route of entry is via the teat duct
--lined by stratified squamous epithelium
-Bacteria colonize and multiply on the surface, cause intramammary infections
-Acute inflammatory response occurs, inflitration with chronic inflammatory cells
-Healing via fibrosis can occur
-Granulomatous mastitis caused by mycobacterium bovis can spread to humans in raw milk

Front 158

Viral Mastitis

Back 158

-Ovine progressive pneumonia virus
--lentivirus
--mastitis in sheep
-Caprine arthritis-encephalitis virus
--lentivirus
--causes mastitis in goats

Front 159

Acute mastitis Histology

Back 159

-Basal lamina is gone
-Neutrophilic and macrophage infiltration
-No more cuboidal/columnar cells lining ducts
-Will get fibrosis with chronicity

Front 160

Basics of Canine Mammary Tumors

Back 160

-Classical presentation
-Older female dog
-Wide range of breeds
-Sexually intact or spayed later in life
-One of more palpable tumors in the mammary chain
--usually more than one gland is affected

Front 161

Risk factors for mammary tumor development

Back 161

-Age
-Hormonal exposure, endogenous or exogenous
-Breed
--smaller breeds live longer and are more likely to develop tumors
-Diet
-Obesity has unknown associated risk

Front 162

Age and Canine Mammary tumors

Back 162

-Older dogs around age 8 and older
-Peak incidence of mammary tumor between 9-11 years old
-Age of onset can vary depending on natural lifespan of breed
-Rare in dogs under 5 unless given exogenous hormones (progestins)
-Lipid-rich secretory carcinomas can be seen in younger dogs

Front 163

Hormones and canine mammary carcinoma

Back 163

-Endogenous ovarian hormones early in life is the most important source and cause of mammary tumor development
-Spay before 1st estrus has 0.05% risk of mammary neoplasm
--no ductal development, no tissue to become cancerous
-Spay before 2nd estrus has 8% risk
-Spay after 2nd estrus has 26% risk
-Spay after 4 years old no protection
-Estrus irregularity, pseudo-pregnancy, and pregnancy have not been found to influence mammary tumor risk

Front 164

Progestins and Mammary tumor risk

Back 164

-Progestin-treated dogs have a significantly increased risk of cancer

Front 165

Diet and Obesity contributing to Mammary tumors

Back 165

-Thinner dogs have decreased risk of mammary tumors
-Obese dogs or dogs fed a high fat diet later in life are not more likely to develop mammary tumors
-Dogs fed a diet high in red meat and dogs obsese at 1 year old are more likely to develop mammary tumors

Front 166

Common clinical presentation of Canine Mammary carcinoma

Back 166

-Commonly have more than 1 tumor
--Close to 70%
-Caudal 2 pairs of glands are most commonly affected
--more mammary and adipose tissue
-Tumors can be large or small, fixed or freely moveable, ulcerated or not
-Best if removed when less than 1 cm
-Lymph nodes may or may not be clinically enlarged

Front 167

Gynecomastia

Back 167

-Enlargement of the mammary gland in the male dog
-Common with sertoli cell tumors

Front 168

Mammary hyperplasia/dysplasia

Back 168

-Duct ectasia, dilated duct that can enlarge and become a cyst
-Lobular hyperplasia (adenosis)
--increase in number of minor ducts or intralobular ducts
-Epitheliosis: intraductal proliferation
-Papillomatosis: proliferation of epithelium without supporting stroma
-Fibroadenomatous change

Front 169

Mammary Duct ectasia vs. ductal cyst

Back 169

Duct ectasia: dilated duct
-less than 5mm

Ductal cyst:
-more than 5mm

Front 170

Mammary gland Lobular hyperplasia
Adenosis

Back 170

-Increase in the number of minor ducts/intralobular ducts
-Can be regular
-Can have secretory activity (lactational)
Can have fibrosis- interlobular fibrous connective tissue
-Can be atypical, nuclei and cells do not look normal

Front 171

Mammary Epitheliosis

Back 171

-Intraductal proliferation
-Affects intralobular ducts
-Proliferation of epithelial cells within the lumen of the intralobular ducts
-Epithelial cells can fill the lumen
-Nuclei are regular, hyperchromatic with little pleomorphism
-Pre-neoplastic change

Front 172

Papillomatosis

Back 172

-Multifocal papilliferous proliferation of the interlobular ducts
-Affects inter lobular ducts
-Papillae are not supported by fibrous stroma

Front 173

Benign mammary neoplasms

Back 173

-Adenoma: simple
-Intraductal papillary adenoma (duct papilloma)
-Ductal adenoma (basaloid adenoma)
--with squamous differentiation
-Fibroadenoma
-Myoepithelioma
-Complex adenoma (adenomyoepithelioma)
-Mixed tumor

Front 174

Mammary Mixed tumor

Back 174

-benign
-Ductal epithelium and myoepithelial cells are neoplastic
-Common in dogs, uncommon in all other animals
-Will have all sorts of tissues developing

Front 175

Intraductal papillary adenoma

Back 175

-Duct papilloma
-Can block duct

Front 176

Tubular carcinoma

Back 176

-When the neoplastic cells infiltrate into the surrounding mammary tissue and illicit a stromal response
-Variations on formation of tubular structure in mammary gland
-Desmoplasia is bad news!

Front 177

Anaplastic Mammary carcinoma

Back 177

-Worst neoplasm in the mammary gland of a dog
-Short prognosis
-Readily metastasize to lymph nodes and lungs
-Infiltrate the lung interstitium
--looks like interstitial pneumonitis

Front 178

Inflammatory Mammary Carcinoma

Back 178

-Clinical term, not pathological
-Looks like it should be mastitis but it is not
-Sudden presentation with edema, erythema, firm and warm mammary gland
-Can occur with or without mammary nodules
-May have erosions and exudates
-Histologically looks like invasion of dermal lymphatic vessels by neoplastic emboli
--blockage of lymphatics
-Metastatic disease!

Front 179

Mammary Osteosarcoma

Back 179

-Malignant transformation of a benign mixed turmor
-Will metastasize by blood to the lungs
-Remove mixed adenomas early so they do not develop into mammary osteosarcoma
--take off when small!

Front 180

Malignant mixed mammary tumor

Back 180

-Carcinosarcomas

Front 181

Fibroadenomatous change in the mammary gland

Back 181

-Proliferation of interlobular ducts and periductal stromal cells
-Stroma is often edematous or myxomatous
-Nuclei exhibit some pleomorphism, mitoses present
-Cells are hyperplastic and dysplastic, not cancerous
-Progestins/Progesterone administration can cause formation
--used for behavior issues in males
--birth control in females

Front 182

Mamamry tumors in Cats

Back 182

-95% are malignant!!
-Assume malignant until proven benign
-Usually are of suubstantial size
-teats do not enlarge

Front 183

Grading of Mammary carcinoma
Tubule formation

Back 183

1. more than 75% of whole carcinoma forms tubules
2. 10-75% of carcinoma forms tubules
3. less than 10% of the carcinoma forms tubules

Front 184

Grading of mammary carcinoma
Nuclear Atypia/pleomorphism

Back 184

1. Nuclei are only slighly larger than normal epithelium
2. Nuclei are distinctly larger, often vesicular, nucleoli are visible
-May have variable size and shape, but not always
3. Markedly enlarged nuclei, often vesicular, prominent nucleoli, marked variation in size and shape

Front 185

Grading of Mammary Carcinoma
Mitotic counts

Back 185

-Count definite mitoses in 10 consecutive high-power fields
1. less than 10 mitoses
2. 10-19 mitoses
3. more than 20 mitoses
-Mitotic frequency score will vary considerably depending on the field diameter of your microscope

Front 186

Final grading of Mammary carcinomas

Back 186

-Add together Tubule formation score, Nuclear atypia/pleomorphism score, and mitotic count score
1. score 3, 4, 5: metastasis is low
2. score 6, 7: gray area
3. score 8 or 9: metastasis is high

Front 187

Features of the Endocrine System

Back 187

-Widely Distributed
-Highly Integrated
-Involved with endocrine signaling
-Under feedback inhibition

Front 188

Feedback Inhibition

Back 188

-Increasing activity at the target tissue decreases the activity of the gland that secretes stimulating hormone

Front 189

Types of Hormones

Back 189

1. Interact with cell surface receptors
2. Diffuse across cell membrane to interact with nuclear or cytosolic receptors

Front 190

Hormones interacting with Cell Surface receptors

Back 190

-Short half-life
-Water soluble
-Polypeptides (insulin)
-Small molecules (epi, norepi)
-Binding to receptor stimulates intracellular signaling molecules
--2nd messengers
-Leads to production of mediators and shifts intracellular Ca
-Influences cell proliferation, differentiation, function, and survival

Front 191

Hormones diffusing across the cell membrane

Back 191

-Interact with nuclear or cytosolic receptors in cell
-Bind to recognition eelements in the DNA
-Steroid hormones: progesterone, glucocorticoids, estrogen
--lipid in cytoplasm, allows diffusion across cell membrane
--long half-life
-Tyrosine derivatives (thyroid hormones)

Front 192

Organs in the endocrine system

Back 192

-Pituitary gland
-Thyroid gland
-Parathyroid glands
-Adrenal glands
-Pancreatic islets
-Paraganglia
-Renal JG apparatus
-Ovary/testis
-Neuroendocrine cells

Always look at both organs when there is a pair!

Front 193

Mechanisms of Endocrine Disease

Back 193

1. Too little hormone
2. Too much hormone
3. Body is unable to utilize the hormone

Front 194

Causes of Too Little Hormone

Back 194

1. Primary hypofunction: sub-normal hormone secretion
2. Secondary Hypofunction: destructive process interferes with secretion of hromone

Front 195

Primary Hypofunction of an Endocrine gland

Back 195

-Sub-normal hormone secretion
-Destruction by a disease process:
--immune-related injury causes hypofunction
--thyroiditis, adrenalitis
--primary inflammation in the gland interferes with function
-Failure of organ to develop
--issue with pituitary decreases GH, leads to dwarfism
-Biochemical defect in the hormone

Front 196

Secondary hypofunction of an Endocrine Gland

Back 196

-Destructive process interferes with secretion of trophic hormone
-Destructive lesion in one organ will result in failure to secrete hormone → hypofunction in target organ
-Pituitary tumor, no releasing hormones, no hormones released

Front 197

Primary Hyperfunction of an Endocrine Gland

Back 197

-Leads to too much hormone produced, increased hormone levels
-Functional tumor in an endocrine gland
--parathyroid adenoma
--islet cell tumor
--sertoli cell tumor
--thyroid adenoma or adenomatous hyperplasia
-Neoplasms secrete hormone in excess of body's ability to degrade the hormone
-Very important mechanism in domestic animals

Front 198

Examples of primary hyperfunction of an endocrine gland

Back 198

1. Parathyroid chief cell adenoma → parathyroid hormone production → fibrous osteodystrophy
2. Beta cell adenoma of pancreatic islet → insulin producion → hypoglycemia
3. Sertoli cell tumor → estrogen production → feminization
4. Thyroid follicular cell adenoma → T4/T3 production → increased BMR

Front 199

Secondary hyperfunction of an endocrine gland

Back 199

-Lesion (usually a functional tumor) in one organ secretes excessive tropic hormone
-Target organ is stimulated → hypersecretion by target organ
-Ex: pituitary gland tumor → ACTH → adrenal cortex stimulation → excessive cortisol

Front 200

Anal sac apocrine gland carcinoma

Back 200

-Functional tumor of non-endocrine tissues
-Mimics natural hormone, stimulates same activity that hormone would
-Causes paraneoplastic syndrome

Front 201

Endocrine Dysfunction secondary to failure of target cell response

Back 201

-Hormone is produced at normal levels but target cell cannot respond
-Defective target
-May be due to lack of adenylate cyclase in cytoplasm or lack of hormone receptors
-Cells of 1st gland will become hypertrophic, no negative feedback and no response from cells

Front 202

Endocrine Dysfunction due to abnormal degradation of hormone

Back 202

-Secretion is normal but blood levels of the hormone are elevated
-Decreased rate of degradation stimulates hyposecretion in endocrine organ
--constant negative feedback

Front 203

Endocrine hyperactivity secondary to diseases of other organs

Back 203

-Hyperparathyroidism that develops secondary to chronic renal failure or nutritional imbalances
-Retention of P and decrease in Ca (Increase in P:Ca ration)
-Leads to parathyroid stimulation
-Decreased kidney fxn leads to decreased vitamin D activation, less Ca absorbed from intestine
→Progressive hypocalcemia
-Causes chronic parathyroid hyperplasia and generalized demineralization of the skeleton
--body wants Ca from skeleton

Front 204

Iatrogenic syndromes of Hormone excess

Back 204

-Administration of exogenous hormone causing functional disturbances
-Prolonged Administration of glucocorticoids → disturbances associated with hypersecretion of cortisol, hyperadrenocorticism → atrophy of adrenal cortex
-Excessive T4/Thyroxine → hyperthyroidism
-Excessive insulin → hypoglycemia

Front 205

Glucocorticoid administration

Back 205

-Iatrogenic cause of hormone excess
-Given to suppress immune system
-Can lead to disturbances associated with hypersecretion of cortisol
--atrophy of the adrenal cortex
-Prednisone, dexmethasome

Front 206

Endocrine Dysfunction due to failure of fetal endocrine function

Back 206

-Leads to prolonged gestation
-Abnormalities in fetal pituitary development can result in prolonged gestation

Front 207

Pituitary gland

Back 207

-Small bean-shaped organ
-Sits in the sella turcica below the brain
-Attached to the hypothalamus by pituitary stalk
-Anterior lobe (adenohypophysis)
-Posterior lobe (Neurohypophysis)

Front 208

Adenohypophysis
Anterior pituitary

Back 208

-Comprises most of the pituitary gland (80%)
-Derived from Rathke's pouch
-Portal vascular system allows transport of hypothalamic releasing hormones from hypothalamus to the pituitary
-Pars distalis: largest, secretes trophic hormones
-Pars tuberalis: wraps around the neural stalk
--capillary network of hypophyseal portal system from median eminence to pars distalis
-Pars intermedia: junction between pars distalis and pars nervosa

Front 209

Pars Distalis

Back 209

-in Adenohypophysis
-Synthesizes and secretes pituitary trophic hormones
-Acidophils:
--Somatotrophs secrete growth hormone
--Luteotrophs secrete luteotropic hormone (Prolactin)
-Basophils:
--Thyrotrophs secrete TSH
--gonadotrophs secrete LH and FSH
-Chromophobes:
--Secrete ACTH and MSH

Front 210

Neurohypophysis
Posterior pituitary

Back 210

-Modified glial cells and axonal processes
-Extend from the nerve cell bodies in the supraoptic and paravenricular nuclei through the pituitary stalk to the posterior lobe
-Secretes ADH and Ocytocin
-Supplied by an artery and drains into a vein, hormones are released directly into systemic circulation

Front 211

Hypothalamic control of the pituitary

Back 211

-All cell populations in the pituitary are controlled by releasing hormones produced in the hypothalamus
-Negative feedback occurs via hormone produced by endocrine gland or specific inhibitory hormones
-Primary center for regulation of body temp, appetite, and seasonal shedding

Front 212

Antidiuretic hormone
ADH
Vasopressin

Back 212

-Produced in supraoptic nucleus
-Released in response to various stimuli
--plasma osmotic pressure
--left atrial distention
--exercise
--emotional states
-Acts on renal collecting ducts and distal nephron
-Increases water resorption from the glomerular filtration
-Counteracts dehydration

Front 213

Oxytocin

Back 213

-Stimulates contraction of smooth muscle in the uterus and myoepithelial cells surrounding the mammary gland ducts

Front 214

Hyperfunction of the Pituitary gland

Back 214

-Neoplasm is the most likely cause
--functional corticotroph adenoma
-Pars distalis adenoma is most common in dogs
-Pars intermedia adenoma is most common in horses
-Different clinical presentations with neoplasms in different areas

Front 215

Functional Corticotroph Adenoma

Back 215

-Causes hyperfunction of the pituitary gland
-Produces excessive ACTH
-Acts on adrenal gland cortex
-Glyconeogenic
-Results in protein catabolism
--atrophy of temporal muscles

Front 216

Clinical findings with Functional corticotroph adenoma

Back 216

-Signs associated with too much cortisol
-Pituitary will be enlarged
--may expand and compress thalamus or hypothalamus → hemorrhage, necrosis, mineralization → CNS signs, blindness, behavioral change, seizures
-Adrenal glands will have cortical hyperplasia, affects zona fasciculata much more than zona reticularis

Front 217

Equine Pituitary Pars Intermedia Dysfunction

Back 217

-Adenoma of pars intermedia
-Associated with Equine Cushing's syndrome
--NOT the same as cushing's syndrome in other animals
-Autonomous production of POMC peptides
-Loss of normal inhibitory control

Front 218

Equine Cushing's Syndrome
Pituitary Pars Intermedia Dysfunction
PPID

Back 218

-Due to pituitary tumor in the pars intermedia
--Autonomously functional chromophobe adenoma
-Associated with autonomous production of pituitary POMC peptides
--loss of normal inhibitory control
-Decrease in dopamine in pars intermedia
--normally inhibits cells (melanotrophs)
-Loss of inhibition of melanotrophs → increased synthesis of peptides → hyperthrphy and hyperplasia → adenoma formation
-Plasma cortisol inhibits ACTH secretion by the pars distalis, but does not affect pars intermedia
-Increased ACTH and other peptides that potentiate ACTH → adrenocortical hyperplasia → cushing's like disease

Front 219

Clinical signs due to deranged hypothalamic function

Back 219

-Excessive POMC derived peptides
-Compression tumor on hypothalamus
-Weight loss, muscle weakness and atrophy
--catabolic effects of cortisol
-Increased susceptibility to infection and poor wound healing
--anti-inflammatory and immunosuppressive effects of cortisol
-PU/PD
-Laminitis
-Hypertrichosis, no seasonal shedding
-Intermittent fever
-Behavioral changes
-Generalized swelling

Front 220

Functional Acidophilic adenoma

Back 220

-Acidophils produce growth hormone
-Occasionally seen in middle-aged to older male cats
-Clinical signs related to increased production of GH
-Leads to Acromegaly

Front 221

Feline Acromegaly

Back 221

-Syndrome of bone and soft-tissue overgrowth
-Insulin resistance due to excessive GH secretion
-New bone deposition → broadening of the face
-Increased weight due to increased muscle/bone/organ mass
-Respiratory stridor due to thickening of airway mucus membranes
-Severe insulin-resistant diabetes mellitus
--due to GH induced insulin resistance
-Death is typically due to renal or congestive heart failure, progressive CNS disease due to tumor enlargement

Front 222

Acromegaly and Diabetes mellitus

Back 222

-Due to GH-induced insulin resistance
-Decrease in target cell insulin receptors
-Decreased receptor affinity
-Undefined post receptor insulin defect

Front 223

Hypofunction of the Pituitary gland

Back 223

1. Compressive Disease
2. Lack of target organ receptors
3. Congenital malformations
4. Prolonged gestation due to dysfunction of fetal pituitary

Front 224

Compressive disease of the Pituitary

Back 224

-Major cause of hypofunction
-Usually Pituitary neoplasia
-Can be functional or non functional
--non-functional: signs due to compression, lack of secretion of trophic hormones
-Can expand and destroy remaining pituitary and hypothalamus
-Pituitary carcinomas are usually non-functional but may result in secondary disturbances
--destruction of anterior and posterior pituitary
--compressive and inflitrative

Front 225

Diabetes Insipidus

Back 225

-Hypofunction of the Pituitary gland
-Caused by inadequate production of ADH or failure of target cells in the kidney to respond to ADH
-Inadequate ADH → drinking and excretion of large volumes of water
-Compression/destruction of neurohypophysis → inadequate ADH production → Diabetes insipidus

Front 226

Nephrogenic Diabetes insipidus

Back 226

-Target cells in kidney cannot respond to ADH
-Congenital lack of adenylate cyclase in cytoplasm
-Secondary Diabetes indipidus can develop in animals with pyometra
-Cells lack target organ receptors

Front 227

Juvenile Panhypopituitarism
Pituitary dwarfism

Back 227

-Congenital malformation of pituitary
-Pharyngeal ectoderm fails to differentiate into hormone-secreting cell populations
-Undifferentiated cells produce fluid, causes large cysts in the sella turcica
-Abscence of adenohypophysis
-Autosomal recessive trait in German Shepherd dogs
--occasionally seen in other dog breeds
-Clinical signs due to growth hormone deficiency
-TSH and ACTH stimulation tests are often normal
--hypothyroidism and hypoadrenocorticism do occur in some cases
-Individual will be normal at birth, then will not grow or grow slowly

Front 228

Clinical signs of Juvenile Panhypopituitarism

Back 228

-Small stature
-Failure to grow, or slow growth
-Failure to gain adult hair coat
-Delayed eruption of permanent teeth
-Delayed epiphyseal closure
-External genitalia will be infantile

Front 229

Pituitary cysts

Back 229

-Can either be due to Juvenile panhypopituitarism (genetic) OR incidental
-Not all cysts are associated with developmental disorders
-Pit cysts are relatively common in dogs but dwarfism is rare

Front 230

Prolonged gestation due to dysfunction of fetal pituitary

Back 230

-Causes hypofunction of the pituitary
-In ruminants is secondary to ingestion of plat toxin
-Veratrum californicum ingestion in early gestation will cause severe cranial malformations

Front 231

Thyroid gland Physiology

Back 231

-Thyroid follicle is the functional unit of the thyroid gland
--Single layer of epithelial cells surrounding protein-rich colloid
-If active, cells are cublidal to columnar with less colloid inside
-If inactive, cells are flattened and more cuboidal with more colloid inside
-C-cells (parafolicular cells) secrete calcitonin to act opposite PTH

Front 232

Thyroid Physiology

Back 232

-Thyroid follicular cells uptake dietary iodine
-Binds thryroglobulin in the lumen, forms Thyroxine (T4) and thriiodothyronine (T3)
--thyroid peroxidase= enzyme that does the binding
-re-uptake of thyroglobulin by thyroid epithelial cells leads to release of T3 and T4 into the bloodstream
-99% of T3 and T4 are bound to plasma proteins in the blood
--Free T3 and T4 are physiologically active
--almost all is bound to proteins
--Anything that changes plasma protein levels will also affect T3 and T4

Front 233

Thyroid peroxidase

Back 233

-Enzyme that binds iodine to thyroglobulin in the thyroid gland
-Allows formation of Thyroxine (T4) and triiodothyronine (T3)
-Can be inhibited

Front 234

T3 vs T4

Back 234

-Triiodothyronine= T3
-Thyroxine= T4
-Both are bound to plasma proteins in blood
-T3 is more physiologically active than T4
-T3 is formed from deiodination of T4
--T4 is converted to T3 in cells

Front 235

Measuring Thyroid Hormone

Back 235

-measure FREE T4
-T3 is unreliable
-Need to know total T4 and free T4 to get an idea as to TSH activity

Front 236

Common Thyroid Diseases

Back 236

1. Hyperfunction: too much thyroid hormone
-More common in cats
2. Hypofunction: too little thyroid hormone
-more common in dogs

Front 237

Feline Hyperthyroidism

Back 237

-Common in older cats
-Multifocal, firm, brown nodules composed of well-differentiated thyroid tissue
-Adenomatous hyperplasia
-Nodules produce thyroxine and negatively inhibit TSH
-Will have increased T4 and T3, decreased TSH
-Leads to thyroid gland atrophy, nodules are producing what the body uses
-Often bilateral
-Will have elevated T4 and T3 levels

Front 238

Feline Hyperthyroidism Clinical Signs

Back 238

-Weight loss with ravenous appetite
-Nervousness, tachycardia
-heat intolerance, HOT animal
-Weakness
-Cardiomegaly, hypertrophy of cardiac muscle
-Arrythmias
-Saddle thromboemboli and death

Front 239

Canine Hypothyroidism Causes

Back 239

1. Lymphocytic thyroiditis
2. Idiopathic atrophy

Front 240

Lymphocytic thyroiditis

Back 240

-Inflammation of the thyroid gland
-Results in canine hypothyroidism
-Immune-mediated
-Thyroid gland is infiltrated by lymphocytes, plasma cells, and macrophages
-Clinical signs start to appear when 75% of the gland is destroyed
-beagles have a genetic component
-Thyroid gland damage leads to release of antigens into circulation
--will see antibodies to thyroglobulin in the blood

Front 241

Idiopathic Atrophy of the Thyroid Gland

Back 241

Leads to hypothyroidism
-Gland can be 1/10 of normal size
-Replaced by adipose tissue and fibrous connective tissue
-May be end-stage of lymphocytic thyroiditis
-Histologically will see adipose tissue and blue areas of blue lymphocytes in the thyroid parenchyma

Front 242

Clinical signs of Canine Hypothyroidism

Back 242

-Slowing of metabolism
-lethargy
-Exercise intolerance
-Heat-seeking animals, always cold
-Mental dullness
-Weight gain
-Bradycardia, slow pulse
-Neuromuscular and reproductive problems
--facial nerve paralysis
-Mild non-regenerative anemia
-Hypercholesterolemia (rare)
--atherosclerosis in dogs usually indicates hypothyroidism
-"Tragic face" because skin is filled with mucin

Front 243

Dermatologic lesions associated with Canine Hypothyroidism

Back 243

-Controversial
-Scaling, bilateral alopecia that may be subtle
--excessive stratum corneum, scales on coat, NOT a crust
--rat tail
-Myxedema if severe
--tragic face, mucin build up in skin
-Secondary infections
--otitis, ptoderma

Front 244

Iodine Deficiency

Back 244

-Most common preventable cause of mental retardation worldwide
-No adequate maternal iodine, fetus and mother are hypothyroid
-no supplemental iodine, fetus may develop cretinism
--mental retardation, deaf-utism, spasticity

Front 245

Goiter

Back 245

-Bilateral enlargement of the thyroid glands due to non-neoplastic and non-inflammatory causes
-Indicates impaired synthesis of thyroid hormone
-Results in euthyroid or hypothyroid state
--thyroid levels can look normal or high

Front 246

Dietary causes of Goiter

Back 246

1. Iodine deficiency
2. Ingestion of goitrogenic substances
--substances that interfere with thyroid hormone synthesis
--Brassica
3. Excessive iodine (rare)

Front 247

Thyroid Carcinoma

Back 247

-Dog issue
-Usually malignant neoplasm
-Can be unilateral of bilateral
-Neoplastic cells break capsule, invade venous vasculature and get to heart and lungs quickly
-Most likely dog is hypothyroid

Front 248

Thyroid adenomas

Back 248

-Incidental findings on post-mortem exam of horses and cats

Front 249

Parathyroid Glands

Back 249

-Internal and external glands
-Embedded in thyroid glands or just crainal to the thyroid glands
-Made of of Chief cells, one cell type

Front 250

Chief cells and Calcium homeostasis

Back 250

-Chief cells produce PTH
-Ca retention, puts Ca into blood
-Increases bone resorption for Ca mobilization
-Dumps P in the kidney, reabsorbs Ca
-Increases active vitamin D in the kidney
-Increases intestinal absorption of Ca

Front 251

Calcitonin

Back 251

-Produced by C-cells in thyroid
-Secreted in response to increased Ca in blood
-Counters action of PTH
-Acts on bone and kidney
-Inhibits bone resorption

Front 252

Cholecalciferol
Vitamin D

Back 252

-Acquired from diet and epidermis
--precursor molecules from UV light
-Epidermis converts provitamin D3 into Vitamin D3
-Vitamin D3 is hydroxylated in the liver then in kidneys to form 1,25 vitamin D3
-Increases absorption of Ca and P form intestines
-Required for mineralization of bone matrix and endochondral ossification in young animals

Front 253

Hyperparathyroidism

Back 253

-Too much Parathyroid hormone
-Primary cause: functional parathyroid adenoma
-Increases blood Ca
-Does not respond to negative feedback, Ca levels in blood stay high
-Signs: anorexia, weakness, PU/PD, stiff gait, pathologic fractures, thickened mandible, loose teeth
-Elevated serum PTH and Ca
-Looks a lot like Anal sac carcinoma or lymphoma

Front 254

Secondary hyperparathyroidism

Back 254

-Caused by chronic renal disease
-Decrease P secretion in the kidney → hyperphosphatemia, increase in P:Ca ratio
-Decreased vitamin D3 → decreased Ca absorbed from intestine
-high P → PTH secretion → parathyroid hyperplasia → release of Ca from bone
-Signs: chronic renal disease
--vomiting, PU/PD, dehydration
--Fibrous Osteodystrophy

Front 255

Pseudohyperparathyroidism

Back 255

-Hypercalcemia of Malignancy
-Anal sac apocrine adenosarcoma
-Lymphosarcoma (most common neoplasm associated with hypercalcemia)
-Parathyroid hormone related protein (PTHrP) is secreted by a tumor
--Malignant tumor of non-parathyroid origin
-PTH will be low, parathyroid glands atrophied

Front 256

Causes of Hypercalcemia

Back 256

-Lymphosarcoma (PTHrP)
-Anal sac apocrine adenosarcoma (PTHrP)
-Malignant tumors growing within bone due to bone resorption
-Malignant neoplasms that metastasize to bone

Front 257

Hypoparathyroidism

Back 257

-Very rare
-Can be iatrogenic with inadvertent removal of parathyroid glands
--can't remove thyroid glands, may take away parathyroid glands also
-Idiopathic: rare in dogs

Front 258

Adrenal gland Removal

Back 258

-Leads to death within just a few days
-K in extracellular fluid becomes elevated
-Urinary excretion of Na is high
-Concentration of Na in extracellular fluid decreases significantly
-Volume of extracellular fluid and blood decrease
-Heart begins to function poorly
--cardiac output declines, shock ensues
-Due to direct loss of mineralocorticoid activity
-Can be prevented by replacement of salts and mineralocorticoids from zona glomerulosa

Front 259

Adrenal Gland Anatomy

Back 259

-Cortex and Medulla
-Cortex has 3 regions
--Glomerulosa: mineralocorticoids
--Fasciculata: glucocorticoids, stimulated by ACTH to make cortisol
--Reticularis: sex hormones
-medulla makes catecholamines (epi and norepi)
-Normal cortex:medulla ratio is about 1:1

Front 260

Gross lesions of the Adrenal Gland

Back 260

-Lesions can be functional and produce cortisol, or non-functional
-Nodular cortical hyperplasia (usually incidental lesion)
-Diffuse cortical hyperplasia (look for primary neoplasm in pituitary)
-Cortical adenomas
-Cortical carcinomas

Front 261

Cortisol

Back 261

-Produced in the Zona Fasciculata of the Adrenal Cortex under ACTH stimulation
-Negatively inhibit ACTH from pituitary and hypothalamus

Front 262

Pheochromocytoma

Back 262

-Neoplasm in the adrenal medulla
-Causes hyperfunction of the adrenal medulla

Front 263

Bilateral adrenocortical hyperplasia

Back 263

-Hyperplastic adrenal cortex, atrophied adrenal medulla
-Due to increased ACTH stumilation
-Results in increased cortisol levels in the blood
-Due to functional tumor in the pituitary
--cranks out ACTH regardless of negative feedback

Front 264

Exogenous cortisol effects on adrenal

Back 264

-Atrophy of adrenal cortex, medulla will be normal
-Exogenous corticosteroids in blood are providing negative feedback to receptors in hypothalamus and pituitary
--less ACTH released
--Less stimulation for cortisol production in adrenal cortex
-Cortisol just isn't needed

Front 265

Primary Adrenal Carcinoma

Back 265

-Opposite adrenal gland will have an atrophied cortex
-Functional tumor is producing unregulated cortisol
--cortisol is inhibiting ACTH release from hypothalamus and pituitary
--no additional cortisol needed
-Atrophy from consistently decreased ACTH levels

Front 266

Non-functional primary adrenal carcinoma

Back 266

-Has no effect on adrenal gland

Front 267

Adrenal medullary tumor

Back 267

-Does not have an effect on the adrenal cortex
-Will increase HR (produces more epi and norepi)
-Does not communicate with the pituitary/adrenal cortex axis

Front 268

Adrenal gland Hyperfuction

Back 268

-Cushing's disease
-Main cause is functional adrenocortical adenoma/carcinoma
-Secondary hyperfunction due to corticotroph adenoma in pituitary

Front 269

Zona glomerulosa

Back 269

-Outer zone of adrenal cortex
-Produces mineralocorticoids
--Aldosterone
-Secretion of mineralocorticoids depends on renin/angiotensin system from kidneys and potassium
-Activation results in increased Na and water resorption → increased renal perfusion
-Not under control of the Hypothalamic-pituitary axis

Front 270

Aldosterone

Back 270

-Produced in zona glomerulosa of the adrenal cortex
-Responds to angiotensin II in the blood
--decrease in renal perfusion
-Stimulates retention of Na and water from the kidneys, results in increased renal perfusion
-Not under the control of the Hypohalamic-pituitary axis

Front 271

Zona Fasciculata

Back 271

-Middle zone of the adrenal cortex
-Produces glucocorticoids in response to increased ACTH release from pituitary
--High levels of corticosteroids will inhibit ACTH release from hypothalamus and pituitary

Front 272

Glucocorticoids

Back 272

-Produced in zona fasciculata of the adrenal glands
-Increase glucose production
-Catabolic effects on fat, muscle, lymphoid and connective tissue
-Suppress immune system, inflammation, and collagen synthesis
--leads to impaired wound healing
-Under control of Hypothalamic-pituitary axis

Front 273

Zona reticularis

Back 273

-Inner zone of the adrenal cortex
-Produces sex steroids and small amounts of glucocorticoids
-Under control of the Hypothalamic-pituitary axis

Front 274

Adrenal Medulla

Back 274

-Made up of chromaffin cells and a few ganglion cells
-Under controol of the sympathetic/parasympathetic nervous system
-Chromaffin cells produce epi and norepi

Front 275

Cushing's Syndrome

Back 275

-Hyperfunction of the adrenal cortex
-Pituitary cushing's syndrome: functional tumor in the anterior pituitary (secondary cushing's)
-Adrenal Cushing's syndrome: functional tumor in the adrenal cortex (Primary cushing's)
-Iatrogenic cushing's syndrome: exogenous corticosteroid use

Front 276

Clinical signs of Cushing's disease

Back 276

-Middle-aged/older animal
-Elevated alkaline phosphatase
-Pot belly, pendulous abdomen due to lack of tone in the abdominal muscles
-PU/PD
-Increased appetite
-hepatomegaly
-Muscle atrophy
-Alopecia and thin skin
-Calcinosis cutis
-increased susceptibility to pathogens
-Diabetes mellitus

Front 277

Feline hyperadrenocorticism

Back 277

-Similar to dogs
-Cats are not usually PU/PD and no steroid hepatopathy
-Often associated with diabetes mellitus due to cortisol-induced peripheral insulin resistance
-May develop severe dermal atrophy and fragile skin
-Can have functional adrenal or pituitary tumors

Front 278

Ferret hyperadrenocorticism

Back 278

-Very common in middle-aged ferrets
-Signs are due to hyperestrogenism
-Due to primary adrenal cortical tumor secreting estrogens
-Serum cortisol is normally low

Front 279

Cushing's disease Classic presentation

Back 279

-Pituitary: Middle aged or older animal
-Adrenal tumor: older female dog
-Increased alkaline phosphatase liver enzyme
-Pot belly
-PU/PD
-Increased appetite
-Hepatomegaly
-Panting

Front 280

Calcinosis cutis

Back 280

-Mineralization of collagen in the skin
-Occurs in dogs only
-Due to long-term exogenous steroids
-Can become osseous plaques over time
-Will get secondary folliculitis as body tries to get rid og Ca

Front 281

Adrenal medullary Hyperfunction

Back 281

-Tumor of medullary chromaffin cells
--Pheochromocytoma
-May cause tachycardia, hypertension, hyperglycemia, vasoconstriction, diffuse sweating
-Clinical signs are hard to document in animals
-Often ends up as an incidental finding
-Benign tumors are more common than malignant
-Malignant tumors metastasize widely, can infiltrate the vena cava

Front 282

Addison's disease

Back 282

-Hypofunction of the adrenal cortex
-Affects all 3 zones
-Adrenal gland will be small and atrophied
--few cells in the capsule
-Most often occurs in female dogs

Front 283

Adrenocortical insufficiency
Hypoadrenocorticism

Back 283

-Idiopathic loss/atrophy of all 3 cortical zones
-Addison's disease
-Thought to be autoimmune disease
-Loss or necrosis of cortical cells and lymphoplasmacytic inflammation leads to cortical atrophy
-Gradual process that waxes and wanes
--exacerbated by stress, no steroids are present to maintain homeostasis
-Clinical signs appear with destruction of 90% of cortices
--have to destroy A LOT of the cortex to get signs

Front 284

Addison's disease clinical signs

Back 284

-Weakness, lethargy
-Collapse
-Weak femoral pulse
-Dehydration
-Bradycardia
-HYpothermia
-Abdominal pain and GI signs (diarrhea)
-Hypontremia and hyperkalemia with unconcentrated urine
-Can present with sudden death
-Zona glomerulosa is KEY for electrolyte balance, no aldosterone no electrolyte balance

Front 285

Clinical signs related to a decrease in aldosterone

Back 285

-Hypovolemia
-Hypotension
-Reduced CO
-Hyperkalemia leading to decreased myocardial excitability
-Increased refractory period, slowing of conduction
-K is so high it is cardio-toxic
-All due to destruction of the zona glomerulosa

Front 286

Clinical signs related to a decrease in Cortisol

Back 286

-GI signs: anorexia, vomiting, abdominal pain
-Weight loss
-Diminished energy metabolism
-Impaired tolerance of stress

Front 287

Secondary Hypoadrenocorticism

Back 287

-Loss of 2 adrenal cortical regions
-Due to long-term exogenous corticosteroids
--Negative feedback to HPA, decreases ACTH, causes atrophy of fasciculata and reticularis
-Lysodren treatment leading to selective destruction of fasciculata and reticularis
-Renin-angiotensin loop is preserved
-Clinical signs are due to decreased glucocorticoids

Front 288

Endocrine Pancreas Anatomy

Back 288

-Islets of Langerhans cell types:
--Beta cells: produce insulin
--Alpha cells: produce glucagon (counters insulin)
--Delta cells: somatostatin
--F cells: pancreatic polypeptide

Front 289

Insulin

Back 289

-Produced by beta-cells in the exocrine pancreas islets of langerhans
-Increases cell uptake and storage of glucose, AA, fatty acids
-Allows sugar to get into the cells
-Secreted in response to hyperglycemia
-Promotes storage of adipose tissue and prevents fat breakdown
-Promotes anabolic effects of protein synthesis on muscles
-Increases glycogen synthesis, decreases gluconeogenesis
-Functional tumor will cause hypoglycemia

Front 290

Glucagon

Back 290

-Produced in alpha cells in the endocrine pancreas islets of langerhans
-Maintains serum glucose levels, keeps glucose in the blood
-Catabolic
-Balances insulin
-Increases glycogenolysis
-increases lipolysis
-Increases gluconeogenesis
-Functional tumor will cause hyperglycemia

Front 291

Somatostatin

Back 291

-General inhibitory function

Front 292

Diabetes Mellitus

Back 292

-relative or absolute insulin deficiency
--relative deficiency due to target cell receptor issue, insulin is present it just can't get into cells
-Prevents target cell utilization of glucose, no glucose can get into the cells
-May be due to lack of beta cells in the pancreas (no insulin production at all)

Front 293

Hyperfunction of the endocrine pancreas

Back 293

-Most common cause is iatrogenic insulin overdose
--too much insulin leads to hypoglycemia
-Can also be due to a functional tumor of islet cells

Front 294

Beta cell tumors

Back 294

-Insulinoma, islet cell tumor
-Uncommon in dogs, rare in the cat
-Common in ferrets
-Usually small tumors and difficult to find
--blends in with pancreatic parenchyma
-In dogs are usually malignant, metastasize to regional lymph nodes and liver
-In ferrets are usually benign
-Does not occur in horses or cattle

Front 295

Beta cell tumor clinical signs

Back 295

-Incoordination
-Ataxia
-Weakness
-Syncope
-Muscle twitching
-Blindness
-Seizures
-Polyphagia

Front 296

Diabetes mellitus

Back 296

-Need Hyperglycemia and glucosuria for diagnosis
-Insulin is not produced by the beta cells OR cannot get into the target cells
--issue with insulin production
--issue with insulin receptor

Front 297

Type I Diabetes mellitus

Back 297

-Genetic susceptibility
-Immunologic destruction of beta cells leading to insulin insufficiency
--no insulin produced because cells are destroyed
-Circulating antibodies against islet cell components come before hyperglycemia

Front 298

Type II Diabetes mellitus

Back 298

-Insulin resistance and dysfunctional beta cells
--exhausted b-cells, lost target for insulin on cells
-Genetic susceptibility with long lag phase before hyperglycemia
-Exacerbated by environmental factors and obesity
-In humans insulin is not usually used to control disease
--diet, exercise, other glucose lowering drugs

Front 299

Diabetes mellitus in Animals

Back 299

-Characterized as:
--Insulin-Dependent DM: requires insulin
--Non-insulin dependent: does not require insulin
-Familial history is rarely available for animals
-Autoantibodies are not available
-Clinical presentation is often not heloful
-ALL DOGS and 50-75% of cats have insulin-dependent diabetes mellitus

Front 300

Clinical signs of Diabetes Mellitus

Back 300

-Hyperglycemia and glycosureia
--tubular threshold for glucose resorption is exceeded
-Osmotic diuresis, leads to PU/PD
--can also lead to bacterial infections and cystitis
-Polyphagia
-Weight loss, cells are starving, causes fat and muscle catabolism
-Increased lipolysis leading to ketoacidosis
-Cataracts: glucose enters lens of the eye
-Glomerulonephropathy and sclerosis
-Fatty liver due to lack of insulin leading to breakdown of lipids and protein
--increases lipids in hepatocytes

Front 301

Histologic changes occurring with Diabetes Mellitus

Back 301

-Typically no histological changes in islets
-May see loss or decreases size of islets
-Hydropic change of basal cells
-Islet amyloidosis in cats
--can also be incidental

Front 302

Tumors of the Paraganglia

Back 302

-Tumors of chemoreceptors or baroreceptors
-Organs are sensitive to changes in pH, CO2, O2
--aid in regulation of circulation and respiration
-Aortic body tumors: rare
-Carotid body tumors

Front 303

Aortic body tumors
Chemodectoma

Back 303

-Heart Base tumor
-Rare
-Most frequently occur in boxers and boston terriers
--brachycephalic dogs
-Has a space-occupying effect leading to compression of the atria, vena cava
--results in dyspnea, ascites, hydrothorax, and hydropericardium (cardiac tympani)

Front 304

Carotid Body tumors

Back 304

-Arise near the bifurcation of the common carotid artery in cervical area
-Rare tumors
-Not functional but space-occupying

Front 305

Grave's disease

Back 305

-Autoimmune disease
-Anti-Thyroid stimulating hormone antibody binds to TSH receptors on thyroid follicular cells
-Stimulates secretion of thyroid hormone
-Causes diffuse thyroid follicular hyperplasia

Front 306

Anopthalmos

Back 306

-Developmental defect
-defective organogenesis
-Complete absence of the eye or eyes
-Very very rare

Front 307

Buphthalmos

Back 307

-Enlargement and distention of the fibrous coats of the eye

Front 308

Coloboma

Back 308

-Apparent absence or defect of some ocular tissue
-Usually results from a failure of part of the fetal fissure to close
-Most often seen as a notch-like defect of the caudal pole at the optic disc
-Outpouching
-Something did not fuse that should have
-Can see the separation histologically

Front 309

Endophthalmitis

Back 309

-Inflammation involving the ocular cavities and adjacent structures
--uvea, retina

Front 310

Exophalmos

Back 310

-Abnormal protrusion of the eyeball

Front 311

Glaucoma

Back 311

-Group of diseases characterized by an increase in intraocular pressure
-Causes pathological changes in the eye

Front 312

Microphthalmos

Back 312

-Congenitally small eye
-May be associated with other ocular defects

Front 313

Panophthalmitis

Back 313

-Inflammation of all of the structures or tissues of the eye
--including the sclera

Front 314

Phthisis

Back 314

-Shrinking, wastage, and hypotony of the eyeball

Front 315

Synophthalmos

Back 315

-Fused eye, 2 eyes are fused into 1
-Occurs with hellabore ingestion on day 14 of gestation

Front 316

Cystic eye

Back 316

-Optic vesicle remains

Front 317

Tissues in the eye derived from mesenchymal tissue

Back 317

-Corneal stroma
-Corneal endothelium
-Uveal stroma
-Hyaloid artery system
-Choroid
-Orbital cartilage and bone
-Sclera

Tissues undergo a series of migrations, differentiations and atrophies during development of the mature eye

Front 318

Tissues in the eye derived from surface ectoderm

Back 318

-Lens
-Corneal epithelium
-Lacrimal apparatus
-Epithelial portions of the eyelids and adnexae

Front 319

Tissues in the eye derived from Neuroectoderm

Back 319

-Retina
-Optic nerve
-Ciliary body
-Posterior iris

Front 320

Mesenchymal defective differentiation in the Eye

Back 320

-Issue with migration:
--choroidal hypoplasia
--Iris hypoplasia
-Incomplete atrophy of anterior or posterior chamber mesenchyme
--Persistent pupillary membrane
--anterior segment dysgenesis
--Goniodysgenesys
--Persistent hyaloid artery

Front 321

Persistent pupillary membrane

Back 321

-Defect in mesenchymal differentiation of the eye
-Iris tissue/vascular tissue does not go away
-membrane is attached to the cornea
--turns blue and affects water flow across the lens
-May block vision
-Can lead to corneal or lens opacity

Front 322

Goniodysgenesis

Back 322

-Defective mesenchymal development of the eye
-Maldevelopment of the filtration angle
-No trabecular meshwork exists in filtration angle
-Acts as a functional barrier to flow of aqueous humor in the eye
-Can lead to glaucoma

Front 323

Choroid hypoplasia

Back 323

-Defective mesenchymal differentiation
-Induction failure by defective retinal pigment epithelium
-Key defect that results in Collie Eye
--also includes colobomas and retinal separation

Front 324

Iris Hypoplasia

Back 324

-Defective mesenchymal differentiation
-Rare defect
-May occur alone or in conjunction with multiple defects
-Most frequent in horses
-May be inherited
-Associated with cataract and conjunctival dermoids

Front 325

Anterior Segment dysgenesis of the Eye

Back 325

-Mesenchymal defective differentiation
-Multiple anomalies of the cornea, lens, and anterior uvea

Front 326

Persistent hyaloid artery

Back 326

-Mesenchymal defective differentiation in the eye
-May lead to focal cataracts

Front 327

Eyelid defective differentiation

Back 327

-Surface ectoderm defective differentiation
-Abnormal palpebral opening
-Entropion
-Ectropion
-Abnormal cilia
-Imperforate puncta leading to excessive tearing
-Coloboma

Front 328

Corneal defective differentiation

Back 328

-May be ectodermal or mesenchymal defective differentiation
-Microcornea in an otherwise normal globe
-Dermoid
-Corneal opacities

Front 329

Dermoid

Back 329

-Choristoma
-Ectodermal defective differentiation in the eye
-Skin-like differentiation with epidermis and irregular dermis and adnexa
-Haired skin on the eye
-On the corneal or bulbar conjunctival surface

Front 330

Congenital Corneal opacities

Back 330

-Usually caused by congenital anterior synechiae and persistent pupillary membranes
-Also caused by edema and non-cellular deposits

Front 331

Lens defective differentiation

Back 331

-Ectodermal defective differentiation
-Aphakia
-Microphakia
-Lenticonus (misshapen lens)
-ectopic lens (misplaced lens)
-cataract

Front 332

Congenital Cataract

Back 332

-Ectodermal defective differentiation
-Associated with other abnormalities or can be alone
-Often due to persistence of mesoderm
-Seen in horses and dogs
-Sometimes hereditary, sometimes not
-Unknown pathogenesis

Front 333

Defective differentiation of the neuroectoderm

Back 333

-Retinal dysplasia
--usually occurs alone
-Optic nerve hypoplasia
--usually occurs with other diseases

Front 334

Retinal dysplasia

Back 334

-Neuroectoderm defective differentiation
-Characterized by retinal folds, rosettes, blending/jumbling of retinal layers, loss of cells, glial proliferation
-Seen most commonly in dogs and cattle
-Caused by:
--failure of proper apposition of the 2 layers of the optic cup
--Failure of induction by RPE
--necrosis or dysplasia of developing retina by viruses (BVDV, Bluetongue, CHV1, panleukopenia, FeLV)

Front 335

Signs of retinal dysplasia

Back 335

-Neuroectoderm defective differentiation
-Retinal folds
-Rosettes
-Blending/jumbling of retinal layers
-Loss of cells
-Glial proliferation

Front 336

Optic Nerve hypoplasia

Back 336

-Neuroectoderm defective differentiation
-Most common anomaly of the optic nerve
-More likely to be atrophy due to destruction of ganglion cells
-Toy dog breeds are most common

Front 337

Inflammatory and degenerative lesions of the eye

Back 337

-Adnexa
-Conjunctiva
-Cornea
-Uvea
-Lens
-Retina
-Optic nerve/sclera/orbit

Front 338

Adnexa

Back 338

-Eyelids and associated glands

Front 339

Inflammation of the eyelids

Back 339

-Anything that affects the skin can affect the eyelids
-Skin diseases
-Blepharitis (inflammation of the eyelid)
-Hordeolum (suppurative adenitis/Stye)
-Chalazion (Meibomian secretion)

Front 340

Hordeolum

Back 340

-Stye
-Localized purulent inflammation of one or more Meibomian glands of the eyelids
-External: occurs on cutaneous surface at the edge of the eyelid
-internal: occurs on the conjunctival surface of the lid

Front 341

Blepharitis

Back 341

-Inflammation of the eyelids

Front 342

Chalazion

Back 342

-Chronic granulomatous inflammation of an eyelid gland
-Meibomian gland inflammation
-Meibomian gland can rupture and release sebum into the surrounding tissue
-Will see macrophages in tissue

Front 343

Dacryoadenitis

Back 343

-inflammation of the lacrimal glands
-Viral-related diseases
--FIP, Canine Distemper, SDAV
-Can be due to malignant catarrhal fever

Front 344

Prolapsed gland of the 3rd eyelid
Cherry eye

Back 344

-gland can be see protruding
-Often is excised, but not recommended
--can contribute to keratoconjunctivitis sicca

Front 345

Cheomosis

Back 345

-Edema of the eye conjunctiva
-Can be severe

Front 346

Distichiases

Back 346

-Presence of a double row of eyelashes on an eyelid
-One or both of the eyelashes are turned against the eyeball
-Can cause corneal irritation

Front 347

Ectropion

Back 347

-Eversion of an edge or margin of the eyelid
-Results in exposure of palpebral conjunctiva
--can predispose to infections

Front 348

Entropion

Back 348

-Turning inward/inversion of an edge or margin of the eyelid
-Piece of the eyelid is turned in towards the eyeball
-Can result in corneal irritation

Front 349

Conjunctivitis

Back 349

-Inflammation of the conjunctiva
-Can be acute or chronic
--Acute: may be due to any noxious stimulus (physical, chemical, allergy, microbial)
-infectious causes
--Chronic: usually due to persistent noxious stimulus
--upper respiratory infections
--herpesvirus
--oncocerca parasite
-Immune-mediated causes
--allergies

Front 350

Immune-mediated Conjunctivitis

Back 350

-Allergy: affects all species and most often dogs
-Eosinophilic conjunctivits
-Ligneous conjunctivitis (linked to plasminogen deficiency)
-Feline lipogranulomatous conjunctivitis

Front 351

Descemetocele

Back 351

-Herniation of Descemet's membrane
-Usually herinates outward through the corneal stroma and epithelium
-May have melanosis
--inundates chronically afected eye

Front 352

Keratitis

Back 352

-inflammation of the cornea
-Inflammatory cells and other components of inflammation arrive through tears or aqueous
--no blood vessels, have to come in with tears
-Specific types of keratitis for each species

Front 353

Keratoconjunctivitis

Back 353

-Inflammation of the cornea and conjunctiva

Front 354

Keratoconjunctivitis sicca

Back 354

-inflammation of the cornea and conjunctiva
-Associated with or due to drying of the conjunctiva
-Usually there is decreased tear production or tears are unable to reach important structures

Front 355

Pannus

Back 355

-Superficial vascularization of the cornea
-Will have infiltration of granulation tissue

Front 356

Cornea Anatomy

Back 356

-Intact cornea is necessary to transmit light and protect deeper eye structures in the globe
-Injury may lead to corneal opacity and loss of clarity
-Epithelium: non-keratinized and non-pigmented
--orderly differentiation
-Stroma: orderly with few cells
--periodicity of stromal collagen is similar to the wavelength of visible light
--No vessels
-Descemet's membrane: thick basement membrane
-Endothelium: pumps out fluids, keeps cornea dehydrated
--Na/K dependent ATPase pump keeps dehydrated

Front 357

Abnormal corneal epithelium

Back 357

-Keratinized and pigmented
-Thickened
-Disorganized
-Opaque

Front 358

Abonrmal stromal collagen

Back 358

-Disorganized
-Thickened
-May be scarred
-May have vascularized keratinocytes
-Increased inflammation
-Melanin, iron, and Ca pigments

Front 359

What can go wrong with the Cornea

Back 359

-Edema: fluid in stroma will increase thickness
-Erosion: erodes epithelium
-Ulcer: damage beyond the epithelium
--will have neovascularization and granulation tissue formation
--Cornea will become keratinized and pigmented

Front 360

Pathology of Corneal Rupture

Back 360

-Stimulus → erosion or loss of epithelium → edema → inflammation → ulcer (scar) → neovascularization (scar) , granulation tissue, fibroplasia → deep corneal stromal ulcer (scar) → desmetocele that extends to decemet's membrane, causes outward pressure → corneal rupture

Front 361

Causes of Corneal Injury and Opacity

Back 361

-Chemicals: caustics, NH3, medications
-Physical: cold, heat, penetrating objects
-Microbial: bacteria, viruses, fungi
-Immunologic: type III hypersensitivity
-Glaucoma: increased intraocular pressure
-Lysosomal storage diseases

Front 362

Corneal edema

Back 362

-Reaction to cornea injury
-Cornea becomes thickened and opaque due to increased stromal fluid
-Fluid is from damaged endothelium or from tears that go through damaged epithelium

Front 363

Corneal erosions and ulcers

Back 363

-Loss of epithelium
-Ulcers can result in secondary bacterial infections
--pseudomonas, strep

Front 364

Corneal Endothelial Dystrophy

Back 364

-Common in boston terriers, Chihuahuas, Dachshunds, and others
-Causes progressive bilateral corneal edema
-Lack of normal vasularization leads to edema
-Feline sequestrum
-Canine persistent ulcer syndrome

Front 365

Corneal Deposits

Back 365

-Can be congenital or acquired
-Pigment: melanin, iron, Ca
--usually occurs secondary to injury
-Lipidosis: cholesterol, lipid, macrophages
--primary or secondary to hypercholesterolemia or corneal injury

Front 366

Corneal Degeneration

Back 366

-Corneal lesions characterized by non-inflammatory loss of epithelial or stromal cells

Front 367

Feline Corneal sequestrum

Back 367

-Discrete orange brown discoloration of the central cornea
-Common in persian or himalayan cats
-Necrosis of stromal cells
-Sequestrum will eventually slough and heal by granulation tissue
-May be an uncommon result of corneal ulceration in cats

Front 368

Canine persistent ulcer syndrome

Back 368

-Recurring ulcers
-Shallow central corneal erosion
-Lesion does not heal, repeatedly re-ulcerates
-Epithelial cells are unable to anchor

Front 369

German Shepard Keratitis

Back 369

-Pannus keratitis
-Idiopathic lesions
-Stromal mononuclear infiltrate

Front 370

Canine Keratitis

Back 370

-Keratoconjunctivitis sicca
-Consequence of inadequate tear film
-Chronic, progressive inflammation
-Idiopathic

Front 371

Feline Herpes Keratitis

Back 371

-Herpes keratitis due to FHV1
-Causes latent infection in adults
-Often unilateral
-May not have associated respiratory signs
-Ulcers and stromal keratitis

Front 372

Feline Eosinophilic Keratitis

Back 372

-Proliferative, "fluffy" white lesion
-Mix of macrophages, fibroblasts, and eosinophils

Front 373

Equine keratitis

Back 373

-Mycotic keratitis
-Destructive, suppurative, deep stromal inflammation
-Aspegillus is the most common pathogen

Front 374

Cattle Keratitis

Back 374

-infectious bovine keratoconjunctivitis
-"Pink eye"
-Caused by Moraxella bovis
-May have concurrent infections
-Shallow central ulcer
-Abscess and malacia also present

Front 375

Sheep and goat keratitis

Back 375

-Infectious keratoconjunctivits
-Contagious opthalmia
-Mycoplasms and Chlamydophila psittaci may be important agents

Front 376

Corneal injury pathogenesis

Back 376

-Noxious stimulus → Erosion/loss of epithelium or endothelium
-Can be repaired and return to normal
-Can also lead to edema, which then repairs and returns to normal
-Edema → inflammation → Ulcer → Neovascularization → Scar and vascular "ghosts" → desmetocele, phthisis bulbi → corneal rupture
-Repair can occur at any stage
-End result of injury depends on severity and chronicity of injury AND ability of the cornea to respond
-Some stages of repair can still end up with scarring

Front 377

Aphakia

Back 377

-Absence of the lens
-Can be congenital or acquired
-Lens is just missing!

Front 378

Cataract

Back 378

-Opacity of the crystalline lens
-Can be due to age
-Can be secondary to intraocular disease
--uveitis, tumors, glaucoma, retinal degeneration, trauma, metabolic disease
-Occurs in diabetic dogs
-May be hereditary in dogs and horses

Front 379

Lenticonus

Back 379

-Conical protrusion of the substance of the crystalline lens

Front 380

Microphakia

Back 380

-Abnormally small crystalline lens

Front 381

Nuclear Sclerosis

Back 381

-Age related compression o the lens fibers
-Causes central lens opacity or tranlucency

Front 382

Chorioretinitis

Back 382

-Inflammation of the choroid and retina

Front 383

Severe chronic keratitis

Back 383

-Dry eye
-Diffuse uptake of fluorescein stain

Front 384

Ulcerative keratitis Histology

Back 384

-Epithelial layer is destroyed, complete perforation of the cornea
-Will have fibroblast proliferation
-Infiltration of inflammatory cells

Front 385

Uveitis

Back 385

-Common in most domestic animals
-Anterior uveitis: iris, ciliary body, usually anterior and posterior chambers are involved
-Posterior uveitis: ciliary body, choroid, and usually retina are involved
-Panuveitis: alll structures inside the sclera are involved
--diffuse uveitis

Front 386

Classifications of Uveitis

Back 386

-Serous: protein-rich fluid produces "aqueous flare" (mild)
-Suppurative: usually bacterial, hypopyon
-Granulomatous: fungal, algae, helminths, mycobacteria, lens rupture, idiopathic, lymphoplasmacytic
--most common form of uveitis in cats
--can be due to FIP

Front 387

Canine "Blue Eye"

Back 387

-Caused by Canine Adenovirus
-Can be due to a modified live vaccine
-Diffuse corneal edema
-Convalescent phase or post-cavvine
-Animal develops uveitis and corneal edema (blue eue)

Front 388

Choroiditis

Back 388

-Inflammation of the choroid

Front 389

Hypopyon

Back 389

-Accumulation of neutrophils (pus) in the anterior chamber

Front 390

Iritis

Back 390

Inflammation of the iris

Front 391

Iridocyclitis

Back 391

-Inflammation of the iris and ciliary body

Front 392

Synechia

Back 392

-Adhesion of parts
-Adhesion of the iris to other structures
-Anterior synechia: adhesion of the iris to the cornea
-Posterior synechia: adhesion of the iris to the capusle of the lens
--rarely adhesion of the iris to the vitreous body

Front 393

Infectious Causes of Uveitis

Back 393

-Bacterial infection:
--Bartonella in cats
--can be heatogenous or from penetrating wounds
-Fungal infection: Secondary to mycotic keratitis or part of systemic disease
-Protozoal infection: Toxoplasma gondii
-Parasitic larval migrans: toxocara canis, Dirofilariasis, onchocerca

Front 394

Idiopathic causes of Uveitis

Back 394

-Feline lymphoplasmacytic uveitis
-Unknown etiology
-Possibly due to toxoplasma and bartonella?

Front 395

Immune-mediated uveitis

Back 395

-Lens induced uveitis
--Phacolytic: lymphocytic uveitis associate with cataracts
--Phacoclastic: occurs 10-14 days after lens rupture
-Canine Adenovirus
-Equine recurrent uveitis

Front 396

Equine recurrent uveitis

Back 396

-Periodic ophthalmia
-result of hypersensitivity to exogenous antigen
-Leptospir
-Onchocerca

Front 397

Canine Uveodermatologic Syndrome

Back 397

-AKA Vogt-Koyanagi-Harada (VKH) syndrome
-Akitas are predisposed
-Autoimmune disease
-targets melanin or component protein expressed in melanocytes
-Bilateral granulomatous uveitis

Front 398

Sequelae of Uveitis

Back 398

-Depends on location, severity, and duration of inflammation
-Corneal opacities due to edema, keratosis/fibrosis, inflammation
-Anterior and posterio synechia (adhesions)
-Glaucoma
-Retinal separation or degeneration
-Cataracts
-Pre-iridal fibrovascular membranes
--Formation of granulation tissue
--leads to intraocular hemorrhage
--Can also be caused by retinal separation and ciliary body tumors
-Phthisis bulbi

Front 399

Phthisis bulbi

Back 399

-"End stage eye"
-Hypotonic, shrunken, disorganized eye
-Eye is shriveled up and fibrotic

Front 400

Iris atrophy

Back 400

-Degenerative lesions of the uvea
-Age-related change
-Occurs in several species
-Progressive thinning of the iris stroma that creates "holes" in the iris
-Looks like congenital iris hypoplaisa and colobomas

Front 401

Irido-ciliary cysts

Back 401

-Degenerative lesion of the uvea
-Occur commonly in dogs
-May or may not be clinically significant

Front 402

Lens

Back 402

-Avascular crystalline structure with no nuclei present
-Composed of a capsule, epithelium, and lens fibers
-Changes in lens position can lead to secondary issues
-Most common lesion is opacity (Cataracts)

Front 403

Diseases of the Lens

Back 403

-Cataract
-Nuclear sclerosis
-Positional change
-Phakitis

Front 404

lens Clarity

Back 404

-Determined by the anatomy and physiology of the lens
-Lens is avascular, gets nutrition from aqueous
-35% of the lens is soluble crystalline protein
-Very few (if any) nuclei
-Very few mitochondria
--undergoes anaerobic glycolysis

Front 405

Histologic Changes associated with Cataracts

Back 405

-Morgagnian globules
--denatured lens proteins
-Bladder cells: large cells, result of aborted efforts at new fiber formation
-Fiber degeneration and fragmentation
-Lens epithelial hyperplasia or metaplasia
-Posterior migration of the lens epithelium
-Mineralization of the lens

Front 406

Diabetic Cataract

Back 406

-90% of spontaneously diabetic dogs develop cataracts
-Bilateral condition
-Begins in the cortex at the equator of the lens
-Progresses rapidly over a few weeks

Front 407

Pathogenesis of Diabetic Cataracts

Back 407

-Glucose is major energy source for lens fibers
--via Embden-Meyerhof pathway of anaerobic glycolysis
--Hexokinase is rate limiting enzyme
-With hyperglycemia, hexokinase is saturated and glucose is shunted to other pathways
-Primary alternative is Sorbitol pathway
--occurs when glucose is higher than 90mg/dl
-Sorbitol accumulates and osmotically attracts water
-Leads to hydropic degeneration and rupture of lens fibers
--opacification of lens

Front 408

Nuclear Sclerosis of the Lens

Back 408

-Age-related compression of the lens fibers
-New fiber formation leads to compression
-Does not affect vision

Front 409

Positional changes of the Lens

Back 409

-Ectopic lens
-Subluxation/luxation
--anterior or posterior movement
--Due to zonule rupture
-Configuration: usually congenital

Front 410

Phakitis

Back 410

-Inflammation of the lens
-Can accompany endophthalmitis/panophthalmitis
-Lens proteins are antigenic

Front 411

Papilledema

Back 411

-Hydropic swelling of the optic disc
-Caused by increased CSF pressure, inflammation, decreased intraocular pressure

Front 412

retinitis

Back 412

-Inflammation of the retina
-Usually involves choroid also
-Rare on own, usually occurs with other lesions
-May occur with neurotropic viral infections
-Can occur with RMSF and Ehrlichia canis

Front 413

Scleral Extasia

Back 413

-Bulging of the sclera, usually through a defect (coloboma)

Front 414

Staphyloma

Back 414

-Protrusion of the sclera (posterior) or cornea (anterior)
-Protrusion is lined with uveal tissue
-Results from inflammation

Front 415

Retinal Separation

Back 415

-Separates between photoreceptors and pigmented epithelium
-Ora ciliaris and optic disc remain attached
-Can be artifactual with processing or fixation
-True separation will have hypertrophy of the RPE and protein accumulation in the subretinal space
--can see on histology
-Causes:
--trauma
--inflammatory exudates and transudates
--Neoplastic cells
--Parasites
--Contraction of cyclitis membrane

Front 416

Retinal Degeneration

Back 416

-Atrophy
-Loss of layers of retina, decreased thickness of layers
-All except glaucoma begin in the outer layer and progress inwards
-Starts with photoreceptors → outer nucelar layer → inner nuclear layer → ganglion cell
-Older lesions look similar to each other
--end result is a glial scar that is poorly cellular
-Can be inheritied condition

Front 417

Progressive Retinal Atrophy

Back 417

-Inherited retinal degeneration
-Large group of bilateral retinal diseases in dogs
-Affects more than 100 breeds
-Most are autosomal recessive
-Progresses to blindness unassociated with inflammation
-Ultrastructural and biochemical changes vary between breeds
-Age of onset and speed of progression differ between breeds
-Common in Irish setters, Norwegian Elkhounds, Collies, and mini poodles

Front 418

Nutritional cause of Retinal degeneration

Back 418

-Vitamin C
-Vitamin A
-Vitamin E
-Taurine in cats

Front 419

Causes of retinal degeneration

Back 419

-Inherited disorders
-Senile changes, old age
-Nutritional deficiencies
-Toxic retinopathies
-INjury/trauma
-Diabetes mellitus
-Hypersensitive retinopathy
-Storage diseases

Front 420

Optic Neuritis

Back 420

-inflammation of the optic nerve
-Caused by:
--spread of meningitis or meningoencephalitis
--Spread of endophthalmitis
--Primary viral cause (FIP, Canine distemper)
--Chorionic gliosis, astrocytosis, or axonal degeneration

Front 421

Issues with the Sclera and Orbit

Back 421

-Nodular Granulomaatous scleritis (dogs)
--nodular proloferative inflammatory lesions of the sclera
--behaves like a locally infiltrative neoplasm
-Orbital cellulitis: extension of inflammation from adjacent non-ocular tissues and foreign bodies
-Retrobulbar abscesses: tooth root abscesses, foreign bodies
-Orbital myositis: Occurs in dogs, Ab against type IIM Muscle fibers

Front 422

Glaucoma

Back 422

-Diverse group of pressure-dependant neurodegenerative disorders
-All result in loss of normal function of retinal ganglion cells and axons in the optic nerve
-Ultimately degeneration leads to loss of vision
-Most consistently recognized feature is elevation in intraoular pressure
-Occurs in dogs more often than cats, more often than horses, least often in ruminants

Front 423

Key mechanism for Increase in intraocular pressure

Back 423

-Reduction in capacity for aqueous outflow
-increase in episcleral venous pressure
--from orbital space-occupying lesions

Front 424

Primary Glaucoma

Back 424

-No other ocular disease
-Goniodysgenesis
-Maturity or middle age
-Malformation or malfunction of the filtration angle apparatus
--can be isolated event or part of mesenchymal dysgenesis

Front 425

Secondary Glaucoma

Back 425

-Increase in Intra-ocular pressure due to other ocular disease
-Uveitis
-Synechiae
-Pre-iridal fibrovascular membrane
-Lens luxation
-Intraocular hemorrhage

Front 426

Sequelae of Glaucoma

Back 426

-Depends on duration and severity
-Buphthalmia
-Scleral thinning
-Corneal edema
-Corneal striae, breaks id Descemet's membrane
-Exposure keratitis secondary to buphthalmos
-Lens luxation or subluxation due to zonule damage
-Cataract
-Atrophy of iris and ciliary body
-Retinal Atrophy
-Retinal separation
-Optic disc cupping

Front 427

Squamous cell Carcinoma of the Eyelid

Back 427

-Occurs in cows most often → horses → feline → dogs
-Occurs most often in limbus, then 3rd eyelid, then eyelid
-UV light causes epidermal plaque formation → papilloma → carcinoma in-situ
-Carcinoma can be invasive and metastasize

Front 428

Neoplasia of the Eyelid and Conjunctiva

Back 428

-Squamous cell carcinoma
-Meibomian gland neoplasms
-Melanocytoma
-Hemangioma/Hemangiosarcoma
-Mast cell tumors
-Adenocarcionma of the 3rd eyelid
-Lymphoma
-Papillomas

Front 429

Meibomian gland Neoplasms

Back 429

-Adenomas are very common in dogs
--70% of eyelid tumors
-Carcinomas are rare

Front 430

Eyelid/Conjunctival Melanocytoma

Back 430

-Common in dogs

Front 431

Eyelid/Conjunctival Hemangioma/Hemangiosarcoma

Back 431

-Occurs in dogs, cats, and horses
-May also be related to UV light

Front 432

Melanocytoma/ Malignant melanoma Intraocular neoplasms in the Dog

Back 432

-prognosis based on histological criteria
--Anaplasia, mitoses, invasion
-Occurs on the iris
--90% are benign
-Choroid: rare and usually benign

Front 433

Melanocytoma/Malignant Melanoma Intraocular neoplasm in the Cat

Back 433

-Diffuse iris melanoma is more common than solitary masses
-May obstruct filtration angle and cause glaucoma
-Long-term neoplasms have greater risk for distant metastasis

Front 434

Iridociliary adenomas and carcinomas

Back 434

-Most common primary tumors of the eye after melanomas

Front 435

Feline post-traumatic sarcomas

Back 435

-Arise from metaplasia of lens epithelium after injury
-Very aggressive neoplasia
-REMOVE NEOPLASTIC EYE!
--any sarcoma will go right back to the brain if it metastasizes

Front 436

Metastatic Neoplasia to the Eye

Back 436

-Lymphoma (most common)
-Pulmonary carcinomas (rare in cats)
-Almost all other neoplasms are possible to metastasize to the eye

Front 437

Medulloepitheliomas

Back 437

-Very rare

Front 438

Orbital Neoplasms

Back 438

-Optic nerve meningioma
-Sarcomas
-Carcinomas (lacrimal adenocarcinoma)

Front 439

REasons for bringing a pet to the vet

Back 439

1. Ear infection
2. Skin allergy
3. Upset stomach
4. Benign tumors
5. Bladder infection
6. Skin infection

LOTS of skin reasons!

Front 440

Skin function

Back 440

1. Barrier function (enclosing, microbial, thermal, chemical, photoprotection, immunoregulation)
2. Sensory perception (touch, heat, pain, cold)
3. Storage (electrolytes, fat, protein)
4. Temperature regulation
5. Vitamin D synthesis
6. Indicator of general health and internal disease

Front 441

Vitamin D synthesis in the Skin

Back 441

Sunlight hits the epidermis, converts provitamin D3 (7-dehydrocholesterol) to Vitamin D3 (Cholecalciferol)
-Vitamin D3 is hydroxylated in liver → 25-hydroxy D3 and in kidneys to active form of 1,25- Vitamin D3
-Redulates epidermal differentiation and proliferation
-Important for Ca absorption from the gut

Front 442

Structural components of the Skin

Back 442

-Epidermis
-basement Membrane
-Dermis
-Adnexal structures
--Hair follicles, apocrine glands, exocrine glands, sebaceous glands, errector pili muscles
-Subcutis/hypodermis
--does not exist in all areas

Front 443

Skin as an enclosing barrier

Back 443

-TIGHTLY regulates water within the body
-Keeps water in and pathogens out
-Number one goal is to prevent water loss
-Prevents loss of elecctrolytes
-Prevent loss of cells
-Protect the animal from environmental insults
--microbial
--thermal
-chemical

Front 444

Epidermis Composition

Back 444

-Keratinized stratified squamous epithelium
-85% keratinocytes
-3-8% Langerhan's cells
-5% melanocytes (always in basal layer
-2% Merkel cells

Front 445

Epidermal thickness

Back 445

-Depends on species
-Thickness depends on contact with the environment
--thin epidermis on abdomen
--thick epidermis on footpads

Front 446

Skin Adnexal Structures

Back 446

-Hair follicles
-Apocrine glands
--epitrichial, near the hair follicle
-Eccrine glands
--atrichial, on foot pads)
-Sebaceous glands
-Arrector pili msucles

Front 447

Species differences in Epidermis

Back 447

1. Dog: melanin in basal layer
-thin skin
2. Pig: pegs anchor dermis into the epidermis
3. Young human: thick skin
4. Old human: thin skin

Front 448

Keratinocyte function

Back 448

-Structural support
-Contribute to skin immune system
--produce cytokines
--can produce inflammatory mediators with stimulation
--Amplify contact hypersensitivity reactions
-Undergoes differentiation and cornification to allow for barrier function

Front 449

Cornification

Back 449

-Formation of stratum corneum
-Modified form of programmed cell death, modified apoptosis
-Keratinocytes undergo dramatic change in shape, size, and function
--Lose all cytoplasmic organelles
-Move from basal layer to the stratum corneum
-Results in development of a thick cornified envelope, replacement of cell plasma membrane

Front 450

Stratum basale

Back 450

-basal cell layer in the epidermis
-Progenitor cell layer
-Slow-cycling stem cells
-Transiently amplifying cells
-terminally differentiated cells
-Hemidesmosomes anchor basal keratinocytes to the dermis
--Essential function!
-Contains melanocytes

Front 451

Stratum Spinosum

Back 451

-"Sponge" or "Prickle cell layer"
-Keratinocytes become larger, flatten out horizontally
-Desmosomes are prominent and attach cells to each other
-May contain Langerhans cells
-If edematous, can visualize desmosomes

Front 452

Stratum Granulosum

Back 452

-Granular Cell lyaer
-Layer of flattened keratinocytes
-Keratohyalin granules present in the cytoplasm of keratinocytes (basophilic)
-Profilaggrin undergoes proteolysis to form filaggrin
--"Filament aggregating Protein"
--Aggregates keratin filaments
-Layer is present in some domestic animals and not others

Front 453

Stratum Corneum

Back 453

-Horny or cornified layer
-Fully keratinized, anucleate, dead cells
-More than 20 layers thick
--85% protein, 15% lipid
--Keratin acts as "bricks" and lipid acts as "mortar"
-Restricts water movement, reduces water loss
-Prevents pathogen and allergen entry
-decreases exposure to topical drugs and irritants
-Absorbs UV light to protect from free radical oxidation
-Continuously shed

Front 454

Structural support of the Epidermis

Back 454

-Keratin intermediate filaments
--10-25 um
--Provide structural integrity
-Intermediate filaments can be used for diagnostic purposes

Front 455

Process of Cornification

Back 455

1. Lipid Formation
2. Dissolution of the Nucleus and Organelles
-release of proteases, DNAse, RNAse
3. Formation of the Protein Core
-Aggregation of keratin filaments
4. Formation of the cornified envelope
-replace plasma membrane with a protein barrier
5. Desquamation

Dramatic change in size, shape, and function of cells
-70% of water islost

Front 456

Keratinocytes and Inflammation

Back 456

-Keratinocytes produce cytokines
--constitutive production
--can be activated by microbial toxins, trauma, or hypoxia
--can cause systemic effects
-Produce other inflammatory mediators
--neuropeptides, free radicals, prostaglandins, growth factors
-Imoportant for drug metabolism

Front 457

Abnormalities in Cornification process

Back 457

-Leads to hyperkeratisis, clinical scaling, and decreased barrier function

Front 458

Cornification Process
Lipid Formation

Back 458

-Lamellar bodies are formed in stratum spinosum
--Fuse with cell membrane and expel lipid contents into the intracellular space
--at junction of SG and SC layer
-Enzymes modify lipid, make it more hydrophobic
-Lipid acts like glue, adheres corneocytes to each other
--Provide moisture and act as hydrophobic barrier
-"Juice packets" burst at the junction into intracellular space

Front 459

Enzymes in skin that change lipids

Back 459

-In granular cell layer:
--Glycosphingolipids
--Phospholipids
--Hydrolases
-In cornified layer:
--ceramides
--Cholesterol
--fatty acids

Front 460

Cornification Process
Release of Nucleus and Organelles

Back 460

-Proteases, DNAse and RNAse
-Orthokeratisis: normal dissolution, nuclei are cleaved
-Parakeratosis: abnormal dissolution, nuclei are retained
--occurs with increased turnover of the stratum corneum from minor trauma

Front 461

Parakeratosis

Back 461

-Abnormal dissolution of cell organelles and nucleus during cornification process
-Occurs due to increased turnover of the stratum corneum
-Will have retained nuclei
--histologically can see blue nuclei in pink stratum corneum

Front 462

Cornification Process
Formation of the Protein Core

Back 462

-Aggregation of Intermediate filaments
--Keratin fibrils
-Profilaggrin → filaggrin → Packing of keratin fibers to form a thick protein core
--Cross linking keratin filaments
--Can also break down keratin to form AA

Front 463

Cornification Process
Formation of the cornified envelope

Back 463

-Surrounds protein core
-Transglutaminases cross-link small proteins
--involucrin, loricrin
-Small proteins form tough protein shell that replaces cell membrane

Front 464

Cornification Process
Desquamination

Back 464

-Enzymes cleave desmosomes
-pH dependent
-Layers of corneocytes are sandwiched between layers of lipid
-Desmosomes are actively broken down and keratin squames are shed into the environment

Front 465

Hyperkeratosis

Back 465

-Abnormality of the cornification process
-Primary= mutation in one of the enzymes involved in cornification
--Can be lamellar bodies, transglutaminase, or keratin intermediate filaments
-Secondary: occurs due to any insult
--allergic disease, endocrine disorder, parasitic and bacterial infections

Front 466

Ichthyoses

Back 466

-Heterogenous group of diseases that are all characterized by faulty cornification that results in scaling
-Usually congenital and heritable disorders
-Harlequin ichthyosis: defective lamellar bodies, no lipid in stratum corneum
-Lamellar Ichthyosis: mutation in transglutaminase gene
-keratin 10 mutation: keratin proteins are not made appropriately
-Ichthyosis vulgaris: Abnormal filaggrin expression

Front 467

Langerhans Cells

Back 467

-Skin Immune system function
-Potent antigen processing cells, dendritic cells
-Bone-marrow derived
-Sense environment between cells
-When activated leave epidermis and enter lymphatic vessels
--travel to local lymph nodes to interact with T-cells
-May be increased with some hypersensitivity disorders
--cause contact hypersensitivity
-May be decreased after UV exposure

Front 468

Histiocytoma

Back 468

-Neoplasia derived from langerhan's cells
-Benign tumors, regress on own

Front 469

Melanocytes

Back 469

-In basal cell layer of the epidermis and hair follicles
-Produce melanin
-Transfer pigment via melanosomes to keratinocytes
--Transfer pigment to other cells
-One melanocyte per 10-20 keratinocytes
-Provide hyperpigmentation after injury
--Re-pigmentation is slower than keratinocyte epithelialization, scars are usually hypopigmented

Front 470

Melanin

Back 470

-Produced by melanocytes in the skin and distributed to keratinocytes
-Provides cosmetic pigmentation
-Acts as UV radiation barrier
--absorb UVR and scavenge free radicals from UV light
-Scavenge free radicals

Front 471

Skin disorders due to abnormal melanization

Back 471

-Post-inflammatory hyperpigmentation
-Color dilution alopecia
--black hair follicular dysplasia
--melanocytes do not transfer melanin properly to hair
-Vitiligo
-Melanoma

Front 472

Merkel Cells

Back 472

-Mechanoreceptors in the skin
-have features of epithelial and neuroendocrine cells
-Located in the basal layer of tylotrich pads and hair follicles

Front 473

Basement membrane Zone

Back 473

-Anchors epidermis to the dermis
-Provides protective barrier
-Complex system that keeps epidermis bound to the dermis
-Important in wound healing, nutritional transport, maintaining a functional epidermis
-Site of many pathological processes
-Ulcerative wounds that penetrate below the basement membrane are more likely to heal with scarring

Front 474

Components of the Basement Membrane

Back 474

-Hemidesmosomes: intermediate filaments connect to nuclear membrane of cels
--provide structural rigidity
--have inner and outer plaques
-Lamina lucida: clear zone
-Lamina densa: type IV collagen
-Sublamina densa: anchoring fibrils, type VII collagen

Front 475

Desmosome vs. Hemidesmosome

Back 475

-Desmosomes attach cells to each other
-Hemidesmosomes attach cells to basement membrane

Front 476

Autoantibodies to basement membrane components

Back 476

-Prevent epidermis from being anchored
-Congenital and acquired blistering disorders
-Hair can act as an anchor in some areas

Front 477

Epidermolysis Bullosa Acquista

Back 477

-Acquired antibody to component of collagen in basement membrane

Front 478

Dermis

Back 478

-Provides elasticity and tensile strength to protect skin against injury
-Acts as a scaffold for vessels and nerves
-Composed of collagen, elastin, proteoglycans (glucosaminoglycans)
--collagen and elastin produced by fibroblasts
-Divided into superficial and deep layers
-Also has mast cells, dermal dendritic cells, and lymphocytes

Front 479

Abnormal Collagen in Dermis

Back 479

-Defects in formation can lead to collagen that lacks tensile strength and leads to tearing of skin
-Dietary deficiency in Vitamin C (ascorbic Acid) results in Scurvy
--also get hemorrhages, collagen lines blood vessels

Front 480

Abnormal Elastin in dermis

Back 480

-Prolonged solar exposure causes permanent damage to elastin fibers
--"Solar elastosis"

Front 481

Ehlers-Danlos Syndrome

Back 481

-VERY stretchy skin due to deficient collagen in dermis
-Occurs in Labs
-Skin can tear, and suture will not really fix it

Front 482

Abnormal Ground Substance in Dermis

Back 482

-Mucin deposition/hyaluronic acid in the dermis leads to wrinkles
--"tragic face" with hypothyroidism
-When too much mucin is deposited, can have cutaneous mucinosis

Front 483

Hair follicles

Back 483

-Act as physical and photoprotective barrier
-Provide visual stimulus for sexual attraction
-Aid with thermoregulation
-Role in sensory perception
-Important for wound healing, hair follicle supplies germ cells to heal wound

Front 484

Structure of hair

Back 484

-"Tube in a tube"
-Outer root sheath is continuous with the epidermis
-Outer root sheath surrounds inner root sheath
-Combined, root sheaths surround the hair shaft
-Hair bulb at the base of the follicle contains papilla that is part of the dermis

Front 485

Simple Hair Follicle

Back 485

-Found in humans, horses, cattle, rats, mice

Front 486

Compound hair follicle

Back 486

-Found in dogs, cats
-Composed of few large hairs
--primary/guard hairs
-Large hairs are surrounded by many smaller hairs
--secondary undercoat hairs
-In sheep secondary follicles have secondary follicles, compound compound follicles

Front 487

Anatomical regions of the Hair follicle

Back 487

1. Infundibulum: extends from the opening of the follicle to the insertion of the sebaceous gland duct
2. isthmus: area between the sebaceous gland duct and insertion of the arrector pili muscle
3. Inferior portion: below the arrector pili muscle, contains the bulb of the actively growing hair

-Inflammatory conditions may target specific regions

Front 488

Hair Cycle

Back 488

-Hair grows in cycles, not continuously
-Affected by photoperiod, temperature, hormones, nutrition, genetics
-Hair replacement in dogs and cats occurs as a mosaic pattern
--neighboring hair follicles are in different stages of the hair cycle

Front 489

Stages of the Hair cycle

Back 489

1. Anagen: state of growing hair
2. Catagen: transitional stage
3. Telogen: resting stage, no growth

Front 490

Sinus hairs

Back 490

-Vibrissae, whiskers
-Slow-adapting mechanoreceptors

Front 491

Tylotrich hairs

Back 491

-Rapid adapting mechanoreceptors in normal body hair
-Scattered among normal hairs
-Merkel cells in tylotrich pads

Front 492

Folliculitis

Back 492

-Inflammation of the hair follicle
-Caused by bacteria, demodex mites, or dematophytes (ringworm fungi)
-Results in patchy hair loss

Front 493

3 causes of Folliculitis

Back 493

1. Bacteria (staph)
2. Demodex mites
3. Dermatophytes (ringworm fungi)

Front 494

Furunculosis

Back 494

-Follicular rupture
-Hair is released into dermis
-Body has foreign body reaction to released hair

Front 495

Disorders affecting hair follicles

Back 495

-Folliculitis
-Furunculosis
-Hair follicle dysplasia
-Hair cycling disorders
-Atrophy/miniaturization

Front 496

Hormonal influence on Hair cycle

Back 496

-Hormones that stimulate anagen
--thyroid hormones
--Androgens
-Hormones that inhibit anagen
--glucocorticoids
--Estrogen

Front 497

Sebaceous glands

Back 497

-Holocrine glands: open into the hair follicle
-Sebocytes degenerate to form sebum
--makes skin water repellent
-Give luster to haircoat
-Help maintain normal flora
--bacteriostatic and funcistatic
-Pheremone production
-Provide for markings and sexual attraction

Front 498

Sebaceous gland inflammation

Back 498

-Sebaceous adenitis
-Hair follicles are annealed at the base
-Will have silvery scales on the bridge of the nose
-Hair follicles are cemented together, come out of skin together
-Without sebaceous glands, animal will not have lubricant for hair, leads to hyperkeratisis
-Animal is prone to secondary bacterial infections
-Scaly dog with hair loss and infections

Front 499

Sweat Glands

Back 499

1. Apocrine: epitrichial
-Empty into the hair follicle
-Produce odorless milky fluid composed of proteins and lipids
2. Eccrine glands: atrichial
-Present only in the footpads of carnivores
-Not associated with a hair follicle
-Ducts empty directly onto the surface of the skin

Front 500

Subcutis/Hypodermis

Back 500

-Between the dermis and skeletal muscle below
-COmposed of adipose tissue and loose connective tissue
--Panniculus= adipose tissue
-Metabolic storage pool, protects deeper structures

Front 501

Cutaneous Vasculature

Back 501

-No direct blood flow
-Have 3 inter-communicating plexuses
--Superficial plexus
--Middle plexus
--Deep plexus

Front 502

Elevated Skin Lesions

Back 502

-Papule
-Plaque
-Pustule
-Crust
-Eschar
-Scale
-Vesicle
-Bulla
-Wheal

Front 503

Papule

Back 503

-Elevated bump
-Less than 1.0cm
-Can be follicular or non-follicular
-Small, solid, red/white, and raised

Front 504

Plaque

Back 504

-"Big papule"
-Solid, slightly raised lesion
-More than 1.0cm

Front 505

Pustule

Back 505

-Small circumscribed elevation that is filled with pus
-Has fluid in it
-Rupture will lead to crust formation

Front 506

Crust

Back 506

-Aggregate of inspissated serous debris
-May or may not have WBCs, RBCs, or bacteria
-Superficial pyoderma

Front 507

Scale

Back 507

-Flat plate of stratum corneum

Front 508

Eschar

Back 508

-Crust that forms in association with an ulcer
-Tightly adherent to the skin
--incorporates dermal collagen
--Scab sticks to underlying dermis

Front 509

Bulla

Back 509

-Large vesicle, 1.0cm or larger
-Fluid-filled, translucent elevation
-"Clear blister"

Front 510

Vesicle

Back 510

-Fluid-filled, translucent elevation that is less than 1.0cm
-Small bulla

Front 511

Wheal

Back 511

-Firm, circumscribed, raised elevation in the skin
-Composed of edema
-Often erythematous
-"Mesa," flat-topped lesions caused by edema

Front 512

Planes

Back 512

-Lesions level with the skin surface
-Macule: less than 1.0cm
--color differs from that of the surrounding normal skin
-Patch: same as a macule, but more than 1.0cm

-Flat, deep, bright, hemorrhage, erythema

Front 513

Erosion

Back 513

-Depression in the skin surface
-Loss of all or part of the epidermis
-Does not go past the basement membrane

Front 514

Ulcer

Back 514

-Depression below the skin surface
-Loss of the entire epidermis and at least some of the dermis
-DEEP lesion

Front 515

Comedone

Back 515

-Keratin-filled dilated hair follicle infundibulum
-Also contains sebaceous material with or without microorganisms
-"Blackhead"
-Follicular plugging

Front 516

Alopecia

Back 516

-Gross term for hair loss

Front 517

Lichenification of Epidermis

Back 517

-Thickening of the skin
-Associated with accentuation of the normal skin markings
-Results from a chronic friction or inflammation
--chronic surface trauma
-Can get hyperpigmentation

Front 518

Epidermal collarette

Back 518

-Special type of scale
-Arranged in a circular pattern, usually caused by the roof of a pustule or papule
-Ruptured pustule with rim of scale left
--Hyperpigmentation in the center
-Usually a sign of bacterial infection

Front 519

Follicular Casts

Back 519

-Accumulation of keratin that thightly adheres to hair shafts
-Hairs in the follicle are annealed together by keratin

Front 520

Pruritus

Back 520

-Unpleasant sensation that provokes a desire to scratch

ITCHY SKIN

Front 521

Pathogenesis of Acute Epidermal Trauma

Back 521

-Trauma → cytokine release by keratinocytes → dermal vasodilation, protein extravasation and inflammatory cells surround superficial dermal blood vessels
-Inflammatory cells migrate into the epidermis
-Langerhans cells migrate to the lymph nodes and present antigen
-Adaptive immune response occurs

Front 522

Reaction to Skin injury

Back 522

-Involves the entire cutaneous unit
-Multiple processes/structures are involved in any pathogenic process
-Have to understand the timing of lesion development to understand the lesion
-Use skin biopsies

Front 523

Lifespan of skin lesions

Back 523

-All evolve over time
-Skin biopsies can be used for Dx and direction for therapy
-Thermal burn: 2-3 days will get coagulative necrosis on histology, 7-10 days get dermal fibrosis and scarring
-Pyoderma: papules progress to pustules, then epidermal collarettes
--pustule is short-lived

Front 524

Effects of chronic surface trauma on the skin
Gross lesions

Back 524

-Regionally extensive
-Lichenification is a focal cutaneous thickening/nodule formation
--mayor may not have erosions/ulcers

Front 525

Signs of Chronic surface trauma

Back 525

-Hair loss
-Skin thickening
-Erythema
-Erosions
-Hyperpigmentation
-Scales
-May or may not see crusts

Front 526

Hair follicle chronic trauma

Back 526

-Hyperplasia of the Outer Root sheath
-May or may not have atrophy also

Front 527

Sebaceous gland chronic trauma

Back 527

-Sebaceous gland hyperplasia

Front 528

Apocrine gland chronic trauma

Back 528

-Pores blocked
-Become dilated
-Periapocrine inflammation

Front 529

Dermis chronic trauma

Back 529

-Fibroplasia in the superficial dermis that leads to fibrosis

Front 530

Histopathology of chronic skin trauma

Back 530

-Hyperplasia of skin with formation of rete ridges
-Skin forms a tighter bond to the dermis
-Compact orthokeratotic hyperkeratosis (anuclear)
-May or may not have patchy parakeratotic hyperkeratosis (nuclei retained)
-Hyperpigmentation is common

Front 531

Pattern Diagnosis

Back 531

-Pattern recognition is important for neoplastic and inflammatory disorders
--can see at low magnification
-Pattern corresponds to a list of differential diagnoses
-Diseases tend to produce typical reaction patterns in the dermis
-Method of pattern diagnosis was developed by Ackermann
-Used by pathologists to read and report findings in skin and tumor biopsies

Front 532

Patterns in Dermatopathology

Back 532

1. Perivascular dermatitis
2. Interface dermatitis
3. intraepidermal Vesicular and pustular dermatitis
4. Subepidermal Vesicular and pustular dermatitis
5. Nodular and Diffuse Dermatitis
6. Folliclitis/perifolliculitis and furunculosis
7. Vasculitis
8. Panniculitis
9. Atrophic dermatoses
10. Fibrosing dermatitis

Front 533

Superficial Perivascular Dermatitis

Back 533

Inflammatory cells aggregate around dermal blood vessels
-May have dermal edema and spongiosis
-Generally non-specific inflammatory reaction
-Eosinophilic infiltrate: allergy
-Neutrophilic infiltrate: bacterial

Front 534

Interface Dermatitis

Back 534

-Inflammatory change focused on basal cell layer
-Limited number of potential causes
--Usually autoimmune or hereditary disease
--Immune complex deposition, type II hypersensitivity reaction, auto-reactive cytotoxic T-cells
-Characterized by lichenoid band and hydropic degeneration

Front 535

Intraepidermal Vesicular and Pustular Dermatitis

Back 535

-Intraepidermal fluid-filled spaces due to intracellular or intercellular edema
-Pustules are filled with inflammatory cells, are more common than vesicles

Front 536

Subepidermal Vesicular and Pustular Dermatitis

Back 536

-Vesicles form within or below the basement membrane
-Caused by immunologic or mechanical forces
-Autoimmune or congenital disease

Front 537

Nodular and Diffuse Dermatitis

Back 537

-Usually infectious agent or foreign material
-Nodular discrete clusters or diffuse dense cellular infiltrate
-Neutrophils dominate: bacterial
-Eosinophils dominate: parasitic or allergic-eosinophilic granuloma
-Histiocytes: chronic granulomatous or pyogranulomatous lesions

Front 538

Folliculitis/Perifolliculitis and Furunculosis

Back 538

Front 539

Vasculitis

Back 539

-Inflammatory cell infiltrate within/around the vessel wall
--leukocytoclasia
-Evidence of vascular injury
--endothelial swelling or necrosis, fibrinoid change, intravascular fibrin thrombi

Front 540

Panniculitis

Back 540

-Extension of dermal inflammation
-Damage to adipocytes results in release of lipids
--lipids undergo hydrolysis into fatty acids and glycerol
-Most inflammatory diseases are sterile and idiopathic
-Can also be an infectious agent, foreign body, trauma, vasculitis, or nutritional cause

Front 541

Atrophic Dermatosis

Back 541

-Most often associated with endocrine disorders
-Results in bilaterally symmetrical alopecia, dull, dry hair coat, hyperpigmentation
-Not pruritic

Front 542

Fibrosing Dermatitis

Back 542

-Loss of adnexal units with dermal fibrosis
-Chronic change indicative of prior cutaneous insult

Front 543

Superficial Perivascular dermatitis

Back 543

Inflammatory cells aggregate around dermal blood vessels
-May have dermal edema and spongiosis
-Generally non-specific inflammatory reaction
-Eosinophilic infiltrate: allergy
-Neutrophilic infiltrate: bacterial

Front 544

Acute perivascular dermatitis

Back 544

-Dermal edema with mild inflammatory infiltrate
-Acute inflammation produces edema
-Will have dermal edema and epidermal edema
-Eosinophils present: type I hypersensitivity reaction

Front 545

Chronic Perivascular dermatitis

Back 545

-Lesions of chronic superficial trauma
-Epidermal hyperplasia, increased cell layers in the epidermis
-Acanthosis: hyperplasia of the stratum spinosum ONLY
-Rete ridge formation, projections of epidermis into the dermis

Front 546

Acanthosis

Back 546

-Hyperplasia of the Stratum Spinosum only
-Can see bridging desmosomes
-Indicates edema

Front 547

Hyperkeratosis types

Back 547

-Orthokeratotic hyperkeratosis: normal process
--anuclear hyperkeratosis

-Parakeratotic hyperkeratosis: Abnormal process
--retained nuclei
--increased keratinocyte cell turnover
--Metabolic disease

Front 548

Type I hypersensitivity reaction

Back 548

-Causes Wheal and flare response in skin
-Vascular congestion
-Can be sensitivity to environmental allergens, food allergy, flea allergy, sarcoptic mange

Front 549

Sarcoptic Mange and Dermal reaction

Back 549

-From Sarcoptes scabiei mite
-Transmissible to humans and animals
-Causes severe pruritus on the abdomen, chest, legs, elbows, and pinnae
-Mites burrow into the stratum corneum
-Mites themselves are rarely found

Front 550

Superficial bacterial infections of the Skin

Back 550

-Perivascular accumulation of neutrophils as inflammatory cells undergo transmigration from vasculature into the vascular space
-Causes epidermal pustules and crusts
-Common to have both an allergy and pyoderma

Front 551

Allergic Dermatitis

Back 551

-Perivascular pattern of dermatitis
-Can have secondary complicating factors
--superficial trauma, bacteria, fungal infection
-May have parakeratosis
-Hypergranulosis
-Spongiosis
-Epidermal hyperplasia

Front 552

Disorders associated with perivascular dermatitis

Back 552

-Zinc-responsive dermatosis: poor diet
-Superficial necrolytic dermatitis: liver disease or glucagonoma
-Flea allergy
-mite infestation

Front 553

Zinc-responsive dermatosis

Back 553

-Common in arctic breeds
-Can occur in any breed if animal has poor diet
-Zinc is not absorbed from the gut
-Usually a mild dermatosis
-Crusty, scaly lesions on the face and pressure points
-Perivascular dermatitis with epidermal and follicular parakeratotic hyperkeratosis

Front 554

Superficial necrolytic dermatitis

Back 554

-Skin disorder in dogs with liver disease
-Hepatocutaneous syndrome
-Less likely cause can be glucagonoma
-Caused by lack of nutrition to the skin
-Animal will have sore feet
-Will see parakeratotic hyperkeratosis, acanthosis with intracellular edema in spinous layer
-Hyperplasia of the basal layer keratinocytes
-"red, white, blue" appearance
-Poor prognosis

Front 555

Superficial Bacterial infections in Skin

Back 555

-Perivascular accumulation of neutrophils as inflammatory cells move from vasculature into perivascular space
-Epidermal pustules/crusts
-Common to have both allergy and pyoderma

Front 556

Lethal acrodermatitis of Bull Terriers

Back 556

-Rare

Front 557

Parakeratotic hyperkeratosis

Back 557

-Indicative of increased epidermal turnover
--Fast epidermal turnover
-Can be due to trauma, malassezia infection, and other causes when focal
-If diffuse have a limited number of DDx

Front 558

Causes of Diffuse Parakeratotic hyperkeratosis

Back 558

-Zinc Responsive Dermatosis
-Hepatocutaneous syndrome
-Lethal acrodermatitis of Bull terriers
-Thallium toxicity

Front 559

Interface Dermatitis Overview

Back 559

-Pathological events target the basal keratonocytes and dermoepitermal junction
--no clear junction present
--Band of lymphocytes will be present within the dermis
-Immune complex deposition
-Type II hypersensitivity reaction
-Autoreactive cytotoxic T-cells
-Tends to be more serious

Front 560

Interface Dermatitis Injury tree

Back 560

1. Damage of basal keratinocytes
-Causes atrophic damage that leads to dermatomyositis and vasculitis
-May have multifocal keratinocyte apoptosis, leads to erythema multiforme
--usually due to drug reaction
-Plasma cell rich infiltrate leads to discoid lupus
-Lymphohistiocytic cell infiltrate leads to cutaneous lupus

Front 561

Characteristic changes associated with Interface Dermatitis

Back 561

1. Lichenoid band of inflammatory cells
-obscures dermo-epidermal junction
-Usually lymphoplasmacityc inflammatory cells
2. Hydropic degeneration of basal epithelial cells
-due to intracellular edema

Front 562

Exfoliative cutaneous lupus erythematosus of German Shorthaired Pointers

Back 562

-Lupoid derm
-Severe autosomal recessive disorder
-Generalized scaling with erosions/hair loss and depigmentation
-necrosis of basal epithelial cells

Front 563

Discoid Lupus erythematosus

Back 563

-Localized lupus
-Localized to nasal planum

Front 564

Dermatomyositis

Back 564

-Familial skin disease of young collies, shelties, and crosses
--hereditary
-Interface dermatitis
-lesions seen around the face, tips of ears, and pressure points

Front 565

Erythema multiforme

Back 565

-Acute disorder
-Associated with adverse drug reactions
-less commonly associated with infections and neoplasia
-Lymphocyte-mediated destruction of keratinocytes
--lymphocytes attack keratinocytes at all levels
-Can involve oral mucosa and foot pads
-Can be idiopathic
-Hydropic basal cell degeneration with individual keratinocyte necrosis/apoptosis in all epidermal layers
-Can be a reaction to injectible heartworm medication

Front 566

Acantholysis

Back 566

-Loosening of the spines Gk
-Loss of cohesion between keratinocytes
-Results in formation of clefts, vesicles, and pustules
-Desmosomes are destroyed
-No cohesion between keratinocytes
-Results in SEVERE edema
-Characteristic feature of pemphigus foliaceus
-Caused by type II hypersensitivity
-Autoimmune disease due to autoantibody production to cell adhesion molecules
--antibody-emdiated targeting of cell adhesion molecules
-Can also be caused by bacterial infection with release of proteolytic enzymes and bacterial toxins
-rarely due to dermatophytosis

Front 567

Acantholytic cells

Back 567

-Keratinocytes that separate completely from neighbors
-become round
-Nucleus is round, uniformly stained
-Cytoplasm is eosinophilic
-Small numbers can be seen in superficial bacterial infection
--proteolytic enzymes cleave desmosomes
-Also occur during spongiosis and dermatophytosis

Front 568

Acanthosis

Back 568

-Hyperplasia of the epidermis and stratum spinosum

Front 569

Bacterial cause of Acantholysis

Back 569

-Bacterial infection with release of bproteolytic enzymes and bacterial toxins
-Mild acantholysis, not a lot of acantholytic cells
-Bacteria are usually present
-Small pustules form
--neutrophils in the pustules are necrotic
-Hard to differentiate between bacterial pemphigus and autoimmune pemphigus
--both cause pustules and acantholysis

Front 570

Dermatophytosis causing Acantholysis

Back 570

-Rarely a cause of acantholysis
-Occurs in dogs and horses

Front 571

Intercellular edema

Intracellular edema

Back 571

-INTERcellular edema: spongiosis

-INTRAcellular edema: Ballooning degeneration

Both cause acantholysis

Front 572

Differential Dx for Vesicular/pustular dermatitis

Back 572

1. Autoimmune disorders
-Pemphigus foliaceus
-Pemphigus vulgaris
2. Bacterial infection
-Pyoderma
-Superficial pyoderma
-Impetigo
3. Viral infection
-Contagious pustular dermatitis

Front 573

Pemphigus foliaceus

Back 573

-Autoimmune disorder that can result in vesicular/pustular dermatitis
-Will have healthy neurtophils and no bacteria
-Vesicles appear on face, ears, groin, feet, footpads
--ONLY occurs on haired skin and footpads
-May progress to generalized autoantibody to desmoglein 1
-Diagnose based on pattern and histology
-Large intraepithelial pustules and crusts
--contain non-degenerate neutrophils and acantholytic keratinocytes without bacteria or fungi
-Antibody is in desmosomes adhesion complex

Front 574

Desmoglein 1

Back 574

-Cadherin group of adhesion molecules in desmosomes
-Attacked by autoantibodies to form pemphigus foliaceus

Front 575

Pemphigus vulgaris

Back 575

-Autoantibody to desmoglein 3
-Acantholysis occurs above the basal cell layer
-Results in vesicle formation
-Basal cells remain attached to the basement membrane via hemidesmosomes
-Gives "tombstone" effect histologically
-Occurs in oral cavity mucocutaneous junction
-Acantholysis with suprabasilar clefting
-Treat with immunosuppressive drugs
-Less often pustular, more often get ulcers

Front 576

Pyoderma

Back 576

-Bacterial infection of the skin
-Can be primary or secondary
-May result inIntraepidermal vesicular/pustular dermatitis
-Can be due to environmental or food allergies, flea allergy

Front 577

Superficial pyoderma

Back 577

-bacterial infections that involve the epidermis and follicular epithelium
-Pustules are usually small and contain necrotic cell debris

Front 578

Impetigo

Back 578

-Type of superficial pyoderma
-Occurs in puppies or immunosuppressed adult dogs
-Sparsely haired skin is affected
-Usually caused by staphylococcus pseudointermedius
-Large intrapeidermal pustules containing degenerate neutrophils, some acantholytic cells, and bacterial cocci
-Causes Vesicular/pustular dermatitis

Front 579

Viral infection as a cause of Vesicular/pustular Dermatitis

Back 579

-Contagious pustular dermatitis
-Contagious ecthyma, orf, scabby mouth
-Parapox infection in sheep and goats
-Vesicles are transient
-Epidermal hyperplasia with edema and intracytoplasmic inclusion bodies

Front 580

Pemphigus folieceous vs. Pemphigus vulgaris

Back 580

-Foliaceous: in haired skin
--Desmoglein 1 is present throughout entire skin layer, autoantibodies to DSG1
--Desmoglein 3 is only present at the bottom
--3 can compensate for 1 when it is attacked by autoantibodies, can cover if 1 is attached by autoantibodies
-Vulgaris: Mucus membranes
--Desmoglein 1 only exists in upper part of skin, DSG3 throughout the skin
--When Desmglein 3 is attacked, 1 cannot compensate to keep skin together
--deep layers are affected

Front 581

Pemphigus Foliaceous vs. Pyoderma

Back 581

-PF: larger pustules that span several adnexal units
--crusts also present
--"Healthy" neutrophils
--No bacteria present
--LOTS of acantholysis

-Pyoderma: bacteria is present along with necrotic cellular debris and neutrophils
--usually smaller pustules
--minimal acantholysis

Front 582

Blistering Disorders of the Basement Membrane Zone

Back 582

-Auto-antibody formation (autoimmune)
--Bullous pemphigoig
--Hemidesomsomal protein
-Congenital defect
--Epidermolysis bullosa, junctional and dystrophic

Front 583

Epidermolysis Bullosa

Back 583

-Congenital or acquired disorder
-Causes subepidermal vesicular dermatitis
-Affects structural integrity of the epidermis at the basement membrane zone
-Results in oral mucosa sloughing especially in areas with increased mechanical trauma
-Epidermis does not stay adhered to the dermis
-Acquista: due to auto-antibody to collagen VII
-Junctional: due to congenital abnormality in hemidesmosomal proteins

Front 584

Cell types in Nodular/Diffuse Dermatitis

Back 584

-Neutrophils: bacterial cause
-Eosinophils: parasitic or allergic cause
-Histiocytes: chronic granulomatous or pyogranulomatous lesions
--mycoabcteria, fungal, or foreign body

Front 585

Bacterial skin diseases associated with Nodular/Diffuse Dermatitis

Back 585

-Mycobacterial granulomas: cutaneous nodules of granulomatous inflammation
--Acid-fast organisms within epithelioid macrophages
--Actinomycosis, Nocardiosis

Front 586

Systemic funcal diseases with cutaneous forms

Back 586

-Blastomycosis (Blastomyces dermatitidis)
-Saprophytic soil organism often located near water
-In young male sporting breeds will cause systemic disease
--weight loss, dyspnea, ocular disease

Front 587

Protozoal disease associated with Nodular/diffuse Dermatitis

Back 587

-Leishmaniasis

Front 588

Non-infectious Diffuse/Nodular Dermatitis

Back 588

-Eosinophilic granuloma
-Localized erythematous plaque
-On medial inguinal area, oral cavity
-Large raised lesions due to hypersensitivity reaction
-Allergic phenomenon
-Diffuse eosinophilic dermatitis with granulomatous response surrounding hypereosinophilic dermal collagen
-Associated with allergic skin disease in cats

Front 589

Perifolliculitis

Back 589

-Inflammation around the hair follicle

Front 590

Folliculitis

Back 590

-inflammation in the hair follicle

Front 591

Mural folliculitis

Back 591

-Inflammation targeting the wall of the hair follicle

Front 592

Furunculosis

Back 592

-Follicle rupture within inflammation
-Foreign body reaction to keratin in the dermis
-lesions often progress from folliculitis to furunculosis
-Rupture can carry bacteria with it
-AKA deep pyoderma

Front 593

3 major causes of folliculitis

Back 593

1. bacterial
2. dermatophyte (ringworm)
3. Demodex mites

Front 594

Bacterial folliculitis

Back 594

-Staphylococcus pseudointermedius is commonly isolated
-Usually secondary to another primary disease
-May result in furunculosis

Front 595

Dermatophytosis folliculitis

Back 595

-"Ringworm"
-Fungi that utilize keratin in hair and epidermis
-3 genera: microsporum, trichophyton, epidermophyton
-Luminal folliculitis, mural folliculitis (cats and horses), pyogranulomatous furunculosis
-Fungal hyphae and arthrospores in hair follicles and on hair shafts
-Histologically cannot see distinction between the hairshaft and the medulla
--filled with fungus
-Zoonotic

Front 596

Demodex canis

Back 596

-Mites reside in the hair follicle
-Normal skin flora on the face of dogs
-"Cigar-shaped" mites
-Proliferate under states of immunosuppression
--In puppies, juvenile form
--in older dogs, immunosuppressed form
-Causes lymphoplasmacytic mural folliculitis
-Furunculosis is common
-Foreign body reaction is common
-Skin will ave hair loss, hyperpigmentation

Front 597

Other non-infectious folliculopathies

Back 597

-Pattern alopecia
-Cyclic flank alopecia
-Color dilution alopecia
--black hair follicular dysplasia

Front 598

Follicular changes

Back 598

-Outer root sheath can undergo same changes as epidermis
-Folliculitis
-Follicular keratosis
-Follicular Atrophy- different forms
--faded follicles
--excessive trichilemmal keratinization
--miniaturization
-Follicular dysplasia/color dilution alopecia
-Follicular neoplasia

Front 599

Vasculitis

Back 599

-Inflamamtory cell infiltrate within or around the blood vessel wall
-Can have evidence of vascular injury
--endothelial swelling/necrosis, fibrinoid change, intravascular fibrin thrombi
-Often associated with existing disease
--bacterial or viral infection
-Can be due to autoimmune disease or adverse drug reaction
-Commonly idiopathic cause
-Will have swelling and hemoorhage, sometines infarcts
-Can see necrosis of vessel, fibrin with edema in the adjacent tissue

Front 600

Post-vaccinal alopecia

Back 600

-Associated with rabies vaccination
-Local reaction in skin
-Ischemia to hair follicles
-Ischematic change induces telogen in hair follicles

Front 601

Causes of Panniculitis

Back 601

-Trauma
-Foreign body
-Infectious (have to rule out)
-rarely autoimmune
-Often idiopathic and sterile
--immune-mediated process

Firm swellings in the skin with ulcers that weep fluid

Front 602

Hyperadrenocorticism and Atrophic Dermatoses

Back 602

-Due to increased endogenous glucocorticoids or exogenous administration of glucocorticoids
-Results in atrophy of epidermis, hair follicles in telogen phase, and follicular hyperkeratosis

Front 603

Topical corticosteroids and skin

Back 603

-Can cause atrophy of skin

Front 604

Calcinosis Cutis

Back 604

-Mineralization of dermal collagen
-Hallmark lesion of hyperadrenocorticism
-Indicates long-standing cushing's disease
-Collagen acts as foreign body, extruded out into the skin
-Skin mineralizes and can become bone

Front 605

Dermal Fibroplasia

Back 605

-Proliferation of fibroblasts and blood vessels with new collagen production
--granulation tissue production

Front 606

Dermal Fibrosis

Back 606

-End-stage fibroplasia
-Increased collagen deposition with altered arrangement
-May find a few remaining fibroblasts

Front 607

Anatomical components of the Ear

Back 607

-Pinna
-Ear canal
-Ear drum/Tympanic membrane
-Ossicles
-Eustachian tube
-Vestibular organ with semi-circular canals and otolith organs
-Cochlea
-Auditory nerve

Front 608

Diseases of the External Ear

Back 608

-Otitis externa
-Hematoma
-Pinnal vasculitis/necrosis
-Alopecia
-Dermatological conditions

Epidermis can get hyperplastic
Seruminous glands get hyperplastic
-Increased keratin can cause stenosis of the canal

Front 609

External ear

Back 609

-Auricle/pinna
-Externa acoustic meatus/passageway
-Auricle to the tympanic membrane

Front 610

Inner Ear

Back 610

-Membranous labyrinth
-Utriculus of 3 semi-circular ducts
--contribute to balance
-Saccules
--cochlear duct, hearing

Front 611

Middle Ear

Back 611

-Tympanic membrane
-Bulla
-Ossicles
--malleus, incus, stapes
-Auditory tube/Eustachian tube
--connects tympanic cavity with the nasopharynx

Front 612

Otitis externa

Back 612

-Common pathology in dogs
-Long pinna, hair in the ear canal, and stenotic canals are predisposing factors
--ear can occlude canal
-Inflammation will also decrease the diameter of the ear canal
-Allergic skin disease is also predisposing factor
-Ear mites in rabbits, cats, rats, goats
--otodectes in kittens
--psoroptes in rabbits
-Foreign bodies (kids putting stuff in ears)
--usually unilateral condition
-Endocrine diseases (cushing's)
-Neoplasia
-Microorganisms are linked to situation that permits proliferation of bacteria

Front 613

Pitbull ear canals

Back 613

-Have tiny stenotic ear canals
-Predisposes to otitis externa

Front 614

1st time otitis

Back 614

-Usually due to yeast or bacterial cocci
-Subsequent infections can destroy the natural bacteria in the ear
-Secondary organisms an grow in the wax in the ear
--pseudomonas
--E. coli

Front 615

Tympanic membrane rupture

Back 615

-Can lead to infection
-Will get pus in the middle ear
-Can eventually get pus into the inner ear
--causes balance problems
-Animal will be deaf

Front 616

Aural hematoma

Back 616

-Will have otitis first
-Animal shakes its head so hard a hematoma forms in the ear
--trauma from head shaking
-Small space for blood to pool, can get very large
-Hematoma develops on the concave side o the pinna
-Starts out fluctuant and becomes firm with organization
--leads to disfigurement

Front 617

Vasculitis on pinna

Back 617

-Can be idiopathic or infectious
-Tick-borne lesions
-Post-vaccinal vasculitis in dogs

Front 618

Gross lesions on the External Ear

Back 618

-Severity depends on chronicity and microbial population
-Will have hyperemia, accumulation of cerumen
-Ceruminous gland hyperplasia gives "cobblestone" appearance
-May or may not have purulent discharge and debris
-Stenosis

Front 619

Histopathology of External ear Otitis

Back 619

-Epidermal hyperplasia
-Atrophy of hair follicles
-Hyperkeratosis
-Sebaceous and ceruminous gland hyperplasia
-May or may not have ulcers
-Inflammatory cells present
-Dermal fibrosis
-Ossification

Front 620

Otitis Media

Back 620

-Inflammation of the tympanic cavity
-Usually bactieral cause
--can be acute or chronic
-Can enter middle ear via eustachian tube (pigs,lambs, cats) or punctured tympanum (dogs, cats)
-Animal will have conduction deafness and pain
-Ear looks hyperemic with edema, ulcers, exudate
-Ossicles and tympanum can become lysed
-May have mineralization of necrotic material within the bullae that can spread to the inner ear and mrainstem

Front 621

Guttural Pouch empyema

Back 621

-In horses
-Suppurative inflammation of the guttural pouches
-Streptococcus equi (strangles)
-Want to flush out and culture the pus
-May have to go in and clean out surgically

Front 622

Guttural pouch Mycosis

Back 622

-Occurs in horses
-Fungal infection of the guttural pouch
-Often due to aspergillus
-Can lead to rupture of the internal carotid artery and bleeding out

Front 623

Otitis Interna

Back 623

-Inflammation of the inner ear
--involves cochlea, vestibule, and semicircular canals
-Usually secondary to otitis media
-Bacterial and suppurative
-May ascend the Vestibulocochlear nerve to the brain
--rare
--Can cause focal meningoencephalitis in the pons and medulla
-Animal will have vestibular dysfunction and deafness
--vertigo, nystagmus, nausea, ataxia, torticollis

Front 624

Types of deafness

Back 624

1. Conduction deafness
2. Sensorineural deafness

Front 625

Conduction deafness

Back 625

-Interference with the conduction of sound results in deafness
-Can be due to disease in the external or middle ear
-Caused by inflamamtion, neoplasia, rupture of the tympanum, entrapment of ossicles in granulation tissue

Front 626

Senssorineural deafness

Back 626

-Maldevelopment or degeneration of the sensory organ, 8th cranial nerve, or auditory pathways within the brain
-Usually involves the organ of corti
-Most prevalent type of deafness in animals
-Can be due to Hereditary cochleosaccular degeneration, Senile, or ototoxic causes

Front 627

Hereditary cochleosaccular degeneration

Back 627

-Type of sensorineural deafness
-Complex inheritance pattern
-May be associated with incomplete pigmentation of the hair coat and uvea in dogs, cats, mink, and mice
-Atrophy of the sensory and supporting cells of the organ of corti, saccular macula
-Collapse of the dorsal or lateral walls of the cochlear and saccular membranous labyrinth
-Secondary degeneration of neurons within the spiral ganglion

Front 628

Senile deafness
Presbycusis

Back 628

-Degeneration of hair cells in the organ of corti and loss of neurons from the spiral ganglion

Front 629

Acoustic and Chemical ototoxicity

Back 629

-Deafness due to noise or chemicals
-Chemicals: aminoglycoside antibiotics
--gentamycin, streptomycin, neomycin
--cats are very susceptible
--toxicity is dose-dependent
-Diuretics: furosemide, bumetanide, ethacrynic acid
-Acetylsalicylic acid (asprin)

Front 630

Vestibular Disease

Back 630

-Central or peripheral disease
-Same causes as deafness
--inflammation, neoplasia, trauma, toxins
-Idiopathic cause is common
-Can be associated with otitus or brain tumor
-Clinical signs include head tilt, falling forwards to affected side, ataxia without weakness, nystagmus
-more easily detected than hearing loss
--mild lesions of the inner ear are more often associated with vestibular lesions instead of hearing deficits

Front 631

Neoplasia in the Ear

Back 631

1. Skin tumors on the pinna
2. Ceruminous gland neoplasms
3. Nasopharyngeal and inflammatory polyps
4. Dentigerous cyst

Front 632

Skin tumors on the Pinna

Back 632

-Histiocytoma and plasmocytoma are common
-Squamous cell carcinoma in white cats and sheep
-Trihoblastoma
-Sebaceous gland adenoma/epithelioma

Front 633

Ceruminous gland neoplasms

Back 633

-Develop in animals with chronic otitis
-Modified apocrine sweat glands
-Seen in older dogs and cats
--in dogs most are benign
--in cats 50% are malignant
-Adenomas and carcinomas
-Carcinomas may invade from auditory meatus into a region of the parotid salivary gland or into bone
--usually in the ear canal

Front 634

Nasopharyngeal and Inflammatory polyps

Back 634

-Polyps in ears
-Originate in the Eustachian tubes
-Common in cats
-Connective tissue, blood vessels, lymphocytes covered by stratified to columnar epithelium

Front 635

Dentigerous Cyst

Back 635

-occurs in foals
-draining nodule on the rostral aspect of the base of the pinna

Front 636

Hematopoietic tissue

Back 636

-Primary site of blood cell production in adults
-Hematopoiesis can occur elsewhere also, most often spleen
--extramedullary hematopoiesis
-Flat and long bones in animals
-With age, central areas and distal extremities of bone are replaced with fat (yellow marrow)

Front 637

Bone Marrow Hematopoietic environment

Back 637

-Hematopoiesis takes place between the venous sinuses in the marrow cavity itself
-Reticular cells are specialized fibroblasts
--extend cytoplasmic processes into the hematopoietic spaces
--forms scaffold to support hematopoietic cells
-Osteoblasts, osteoclasts, and flat cells line endosteum
-Stromal cells provide structural support and produce extracellular matrix components
-Adipocytes, macrophages, lymphocytes, plasma cells

Front 638

Hematopoietic cell behavior

Back 638

-Influenced by direct cell-cell and cell-matrix interactions
-Soluble mediators are important
--cytokines and hormones
-Undergo sequential divisions as they develop
--progressively higher numbers of cells as hematopoietic cells mature
-Cells continue to mature after they have stopped dividing

Front 639

Hematopoietic tissue

Back 639

-Highly proliferative and self-renewing
-Gives rise to cells with committed differentiation programs
-Common ancestor of all blood cells

Front 640

Products of Hematopoiesis

Back 640

-Pluripotent stem cell → Myeloid stem cell →
--RBCs
--granulocytes
--Monocytes
--Platelets

Front 641

Erythropoiesis

Back 641

-Formation of RBCs
-Organized series of maturation regulated by Erythropoietin
-Rubriblast → prorubricyte → rubricyte → metarubricyte → polychromatophil → RBC
-Normal development time is about 1 week
-Reticulocytes start maturation in bone marrow and finish in peripheral blood circulation and spleen
--except horses, do not release reticulocytes into circulation

Front 642

Erythropoietin
EPO

Back 642

-Dominant regulator of erythropoiesis
-Glycoprotein
-Acts on early erythroid progenitor cells with other cytokines
-Synthesized in the kidney
-Promotes proliferation of RBCs
-Inhibits apoptosis of RBCs
-Stimulus for increased production is hypoxia

Front 643

Reticulocytes vs. RBCs

Back 643

-RBCs: no organelles
-Reticulocytes: have ribosomes and mitochondria
--make reticulocyte bluish/purple

Front 644

RBCs

Back 644

-Mature reticulocytes
-No organelles
-Take about 1 week to mature
-Last about 150 days in horses and cattle
--100 days in dogs
--70 days in cats
-Production is stimulated by hypoxia and increase EPO synthesis in the kidney

Front 645

Granulocytes

Back 645

-Neutrophils
-Eosinophils
-Basophils
-Monocytes

Important immune functions

Front 646

Granulopoiesis and Monocytopoiesis (Myelopoiesis)

Back 646

-Formation of granulocytes and monocytes
-Initiated by release of inflammatory mediators (IL and TNF-a)
--mediators stimulate fibroblasts, macrophages, and endothelial cells to produce cytokines
--G-CSF and GM-CSF)
-Increase in cytokines G-CSF and GM-CSF result in increased granulopoiesis and monocytopoiesis
-Progranulocyte → myelocyte → metamyelocyte → band cell → neutrophil, eosinophil, or basophil (granulocytes)
-Process takes about 5 days for neutrophils

Front 647

Neutrophil formation and life span

Back 647

-Formation from myeloblast → neutrophil takes about 5 days
-Reserve of fully mature neutrophils is maintained in the bone marrow
-Predominant leukocyte type in the blood of most domestic species
-Only in circulation for less than 12 hours

Front 648

Megakaryopoiesis
Thrombopoiesis

Back 648

-Regulated by Thrombopoietin synthesized mostly in liver
--produced constitutively
-Progenitor cell → endomitosis to become polyploid → extend cytoplasmic processes bone marrow venous sinuses → shed cytoplasmic fragments (platelets) into circulation

Front 649

Thrombopoietin

Back 649

-Synthesized mostly in the liver
-Dominant regulator of thrombopoiesis
-Produced at a constant rate

Front 650

TPO receptor

Back 650

-Expressed by platelets and their precursors
-Binds Thrombopoietin in the plasma
-Platelet mass decreases, less TPO is bound to platelet receptors
--increased concentration of TPO in free plasma stimulates thrombopoiesis

Front 651

Megakaryocytes

Back 651

-Arise from a progenitor cell
-Undergo endomitosis to become polyploid
--8N-32N
-Cytoplasmic processes extend into the lumina of the bone marrow venous sinusoids
-Membrane-bound cytoplasmic fragments are shed into bone marrow venous sinusoids

Front 652

Diagram of Hematopoiesis

Back 652

Front 653

Bone marrow Aspirates
Cytology

Back 653

-Collections of cells smeared on a slide and examined microscopically
-Faster than a biopsy
-More detailed evaluation of internal structures of the marrow
-All you have are cells, no relationships
-

Front 654

Bone Marrow Core Biopsy

Back 654

-Histological preparations
-Sections of tissue that are fixed with formalin or embedded in paraffin/plastic
-Allows for definitice determination of cellularity and fibrosis
-Takes more time
-Fixation can add artifacts

Front 655

General aspects of a Bone Marrow Evaluation

Back 655

-Peripheral demands for WBCs, RBCs and platelets results in rapid shift of bone marrow cytologic profiles
--due to hyperplastic responses
-Changes can be due to blood loss, diseases of bone marrow
--bone marrow responds by making RBCs
-

Front 656

Bone Marrow Evaluation

Back 656

1. Cellularity and Particles
--are bone marrow spicules/particles present?
--Is cellularity increased?
2. Should see all maturation sequences and morphology
--all 3 lines (myeloid, erythroid, megakaryocytic)
3. Frequency of lymphocytes, macrophages, and plasma cells, other cells also
4. Adequacy of Iron
5. Presence of abnormal cells
6. Myeloid:Erythroid ratio calculation

Front 657

Myeloid:Erythroid Calculation

Back 657

-Only erythroid and myeloid cells, NOT megakaryocytes
-Normal M:E in companion animals is 1:1 or 2:1
-Normal M:E in livestock and horses is 0.5:1

Front 658

Common indications for a Bone Marrow Evaluation

Back 658

-Unexplained, persistent increases or decreases in particular cell lines
-Abnormal/immature cells in curculation
-Atypical cellular reactions
-Fever of unknown origin
-Unexplained laboratory findings
-Staging of Malignancies
-Systemic infections
-MUST submit CONCURRENT CBC

Front 659

Indications for a Core Biopsy

Back 659

-Bone changes
--osteosclerosis, osteopenia, osteolytic lesions
-Bone marrow cellularity
--hypocellular, hypercellular, aplasia
-Bone marrow fibrosis
-Focal lesions
-Unsuccessful aspiration biopsy if aspirate is poorly cellular

Front 660

Bone Marrow Hyperplasia

Back 660

-Increase in response to peripheral demand for a specific cell type
-Can be generalized to all cell lines or specific to one cell line
-Predictable increase if animal is not diseased
-Erythroid hyperplasia
-Myeloid hyperplasia
-Megakaryocytic hyperplasia
-Lymphocytosis/plasmacytosis
-Histiocytosis
-Mastocytosis

Front 661

Erythroid Hyperplasia

Back 661

-Usually due to hemorrhage of hemolysis
-Hemorrhage: internal or external blood loss
-Hemolysis: RBC destruction
-Low Hb → hypoxemia → EPO production stimulated → increased erythropoiesis
-Increased in RBC production causes decrease in M:E ratio
--more Erythroid progenitors in marrow
-Immature polychromatic RBCs may appear in peripheral blood

Front 662

Causes of Hemorrhage

Back 662

-Trauma
-Defect in hemostasis
-Neoplasia
-GI ulceration
-Parasitism
-Coagulopathies (inherited or toxins)

Front 663

Causes of Hemolysis

Back 663

-Extravascular hemolysis:
--immune mediated
--hemoparasitism
--toxicity
-intravascular hemolysis:
--immune-mediated (IMHA)
--hemoparasitism
--toxicity
--enzymatic deficiencies
-Oxidant injury
--Hypophosphatemia

Front 664

Polychromatophilic RBCs in Peripheral blood

Back 664

-Indicate hemolysis or hemorrhage
-Polychromasia on CBC
--"reticulocytes" when stained
-Other cell lines stay normal but will be perceived to be decreased due to large expansion of erythroblast population

Front 665

Regenerative anemia

Back 665

-Regeneration can occur
-increased reticulocytes indicates that regeneration is happening

Front 666

Iron stores and blood loss

Back 666

-With acute blood loss Fe stores remain adequate
--demand for RBCs can still be met
-With persistence of blood loss will have depletion of Fe
--Regnerative response is less, eventually results in non-regenerative anemia
-Non-regenerative anemia is secondary to Fe depletion

Front 667

Erythroid Hyperplasia with concurrent myeloid hyperplasia

Back 667

-Acute, severe anemia due to hemolysis or hemorrhage
-Immediate, no time for tissue to respond to insult
-M:E ratio can be normal due to hyperplasia of both cell lines
-Acute disease in Hb → tissue O2 is compromised → tissue necrosis → myeloid hyperplasia to increase macrophages and neutrophils → peripheral leukosis
-RBC line is also increasing to respond to hemorrhage

Front 668

Erythroid Hyperplasia without Anemia

Back 668

1. Chronic O2 deprivation
--altitude, chronic lung or heart disease
2. Hyperthyroidism due to increased metabolic demands for O2
3. Compensated hemolytic disease

-O2 deprivation and Hyperthyroidism can result in a peripheral erythrocytosis (high RBC count)

Front 669

Myeloid Hyperplasia

Back 669

-Response to an increased need for granulocytes or monocytes
-Common with certain types of inflammation
--infection, abscesses, any inflammatory state
-M:E increases, more M than E in blood
-May be a left-shift in granulocyte production within the marrow
--characterized by an increase in immature forms
-Marrow responds by increasing megakaryocytes
-Will have more immature cells with "left shift" in maturation
-Antigens or endotoxins (inflammatory state) → IL1 released from cells → TNF-a → release of additional factors

Front 670

Megacaryocytic Hyperplasia

Back 670

1. Peripheral destruction (ITP)
2. Platelet loss due to hemorrhage
3. Consumption (DIC)

Front 671

Non-specific increases in Hematopoiesis

Back 671

-Can be due to antigenic stimulation, chronic infections, toxic insults
-Lymphocytosis
-Plasmacytosis
-Histiocytosis
-Mastocytosis
-Increases are not helpful for cytology, have to look for something else

Front 672

Bone Marrow Hypoplasia

Back 672

-Results in a peripheral decrease in that cell type
-Clinical signs reflect missing cell type
-Changes M:E ratio
-Peripheral cytopenia indicates abnormal response
--low numbers of cells
-Can be measurable hypoplasia of one or more cell lines or a failure to respond with appropriate hyperplasia
-No response to peripheral changes is abnormal

Front 673

Bone Marrow Hypoplasia due to chronic disease or inflammation

Back 673

-Most common cause of non-regenerative anemia
-M:E is normal or slightly increased
-Marrow-based disease, marrow does not respond to insult/injury and make new RBCs
-Can be due to:
-- immune-mediated targeting of hematopoietic cells
--Cytotoxicity or drug-induced
--Infection (Parvovirus, FeLV, FIV)
--Endocrine-induced (hyperestrogenism, hypothyroidism)
--Iron deficiency (loss of Hb addition to RBCs)
--Renal failure (decreased EPO)
--Malnutrition
--Idiopathic

Front 674

Hepcidin

Back 674

-Acute-phase protein
-Synthesized in the liver
-Expression increases with inflammation, infection, or Fe overload
-Decreases with anemia or hypoxia
-Limits Fe availability
-Binds to and degrades cell surface iron efflux molecule (ferroportin)
--causes functional Fe deficiency
-Inhibits absorption of dietary Fe from GI
-Inhibits export of Fe from macrophages and hepatocytes into the plasma

Front 675

Inflammatory cytokines contributing to anemia

Back 675

-TNF-a and IL-1
-INhibits erythropoiesis by oxidative damage
-Triggers apoptosis of developing erythroid cells
-Decreases expression of EPO, EPO receptors, and stem-cell factor

Front 676

Bone Marrow Inflammation

Back 676

-May not be recognized in bone marrow aspirates
--inflammatory cells are normal component of marrow
--inflammation can be focal and missed in sampling
-Acute myelitis
-Granulomatous or pyogranulomatous

Front 677

Acute Bone Marrow Myelitis

Back 677

-Fibrinous and neutrophilic
-Dogs and cats with non-regenerative IMHA can have bone marrow inflammation with fibrin deposition, edema, and neutrophils

Front 678

Granulomatous or Pyogranulomatous Bobe Marrow Myelitis

Back 678

-Diffuse or multifocal increase in macrophages and epithelioid macrophages

Front 679

Myelodysplastic syndrome

Back 679

-Hematopoietic neoplasia
-Defect in myeloid stem cell, issue within the marrow
-Clonal myeloid proliferative disorder
-Ineffective hematopoiesis
-Results in peripheral cytopenia of the affected cell populations
-Hyperplasia of one or more cell line without change in the peripheral cell count
-Can precede development of acute myeloid leukemia
-Blast cell % is higher than normal but not higher than 20%
--more than 20% = leukemia
-Rare in veterinary medicine, most often occurs in cats with FeLV

Front 680

Leukemia

Back 680

-Umbrella term for malignant hematopoietic neoplasms that originate in the bone marrow
-Typically have significant numbers of neoplastic cells in the blood
-Can refer to other forms of neoplasia originating outside of the bone marrow that progress to include bone marrow and blood
-Lymphocytic or myelogenous
-Acute or chronic based on degree of differentiation of neoplastic cells

Front 681

Acute Myeloid leukemia

Back 681

-Progressive anemia, decrease in functional leukocytes, or thrombocytopenia
-Peripheral blood smear detects blast cells
-Marrow blasts of myeloid origin are more than 20% of all nucleated cells
--lack of maturation
-Extremely poor prognosis
-Mostly seen in cats with FeLV

Front 682

Chronic Myeloid Leukemia

Back 682

-Rare chronic neoplastic disorder
-Very high peripheral cell counts
-Marrow hyperplasia of the affected cell line
-Cells have normal morphology
--Dx by elimination
-Many types of CML

Front 683

Types of Chronic Myeloginous Leukemia in Animals

Back 683

-Chronic granulocytic leukemias of neutrophils, eosinophils and basophils
-Chronic myelomonocytic leukemia
-Mast cell leukemia
-Essential thrombocythemia
--CML of platelet lineage
-Polycythemia vera
--CML of erythrocyte lineage

Front 684

Acute Lymphoid leukemia

Back 684

-Large, immature lymphocytes
--Usually in high numbers of circulating blasts
-May efface the marrow
-Occurs mostly in younger to middle-aged animals

Front 685

Chronic Lymphoid Leukemia

Back 685

-Small, well-differentiated lymphocytes
-Usually do not efface the marrow
-Usually occurs in older animals

Front 686

Multiple Myeloma

Back 686

-Malignant Neoplasm of plasma cells
-Disseminated neoplasm throughout the marrow and spleen
-Usually not "leukemic" but can be
-Well-differentiated or pleomorphic cells
-Associated with production of a single type of immunoglobulin
--monoclonal or M-protein
-Monoclonal population of plasma cells that make 1 type of Ig
-Patient can be hypercalcemic and destroying bone
-Can see "flame cytoplasm" on histology
-Diagnose based on 2 out of 4 criteria:
--Marrow plasma cells greater than 30%
--Monoclonal protein (M-spike)
--Bence-jones protein in the urine
--Lytic bone lesions

Front 687

Other hematopoietic neoplasms

Back 687

-Systemic mastocytosis
-Histiocytic sarcoma
-Metastatic carcinoma

Front 688

Myelofibrosis

Back 688

-Fibrosis of the bone marrow
-Usually reactive to injury, neoplasia, or inflammation
-Generally secondary/reactive to other injury
--sepsis, hematopoietic malignancies, drug toxicity, IMHA
-Difficult to aspirate
-Histologic diagnosis
-Pancytopenia of all cells
-If primary is a myeloproliferative disorder

Front 689

Organs in the Lymphatic system

Back 689

-Thymus
-Spleen
-Lymph nodes
-Lymph nodules
-Bursa of Fabricius (in birds)

Primary lymphoid organ
--animals= thymus and bone marrow
--Ruminants: peyer's patches
--Birds: bursa of fabricius

Front 690

Dense cell aggregates in the body

Back 690

-Tonsils
-MALT/BALT/GALT
-Peyer's patches
-Bone marrow

Front 691

Secondary lymphoid organs

Back 691

-Spleen
-Lymph nodes
-Lymph nodules
-Responsible for immune responses
--produce antibody and cell-mediated immunity

Front 692

Lymphopoiesis

Back 692

-Production of new lymphocytes
-T-lymphocytes= effector cells of cell-mediated immunity
-B-lymphocytes= effector cells of humoral immunity
-Pluripotent stem cell → T-cell or B-cell
-B-cells become plasma cells and produce antibody

Front 693

T-cell development

Back 693

-Originate in Bone marrow, migrate to the thymus to undergo differentiation, selection and maturation
-Once mature migrate to peripheral lymphoid tissue as effector cells
-Prothymocyte (in bone marrow)→ Cortical thymocyte (in thymic cortex) → medullary thymocytes

Front 694

T-cells

Back 694

-50-70% of peripheral blood mononuclear cells
-Located in paracortical regions of lymph nodes and periarteriolar sheaths of the spleen
-Recognize antigen only after antigen processing into peptide fragments and associated with MHC molecules
-CD4 (helper T-cells)
-CD8 (cytotoxic T-cells)

Front 695

B-cell Development

Back 695

-Development occurs in 2 phases
1. Antigen-independent phase in primary lymphoid tissue (bone marrow, ileal Peyer's patches)
--B-cells express IgM and IgD on surface
--Mature B-cells
2. Antigen-dependent phase in secondary lymphoid tissues (spleen, lymph nodes, tonsils, peyer's patches)
--Antigen-activated mature B-cells differentiate into IgM secreting plasma cells or switch to another antibody isotype
-Progenitor B-cell → pre B-cell → Immature B-cell → Mature B-cell

Front 696

B-cells

Back 696

-5-20% of peripheral blood mononuclear cells are B-cells
-Located in lymphoid follicles
-Can recognize soluble antigen

Front 697

NK cells

Back 697

-Bone-marrow derived
-AKA "large granular lymphocytes"
-5-15% of peripheral blood mononuclear cells
-Non-specific cytotoxic cells
--Early response to tumor cells and viral infections
-Cytoplasm has cytotoxic granules with perforin and granzymes
--lyse target cells
-Not HMC restricted
-Do not develop memory cells
-Part of innate immunity

Front 698

Thymus

Back 698

-Maximal mass relative to body size at birth
-Involutes following sexual maturity
-Lymphoid and epithelial components are gradually replaced by loose connective tissue and fat
-Stromal portion is made of epithelial cells (Hassall's corpuscles), macrophages, and dendritic cells
--contribute to microenvironment essential for T-cell development
-Thymocyte portion has T-lymphocytes at different stages of maturation

Front 699

Types of Injury to the Thymus

Back 699

-Congenital
-Lymphoid Atrophy
--infectious agents, toxins, chemotherapeutic agents, malnutrition
-Inflammation
-Hematomas
-Neoplasia
--thymoma
--lymphoma
-Hyperplasia

Front 700

Thymic Cysts

Back 700

-In cranial mediastinum
-Lined by ciliated epithelium
--remnrants of branchial arch epithelium
-Usually incidental finding

Front 701

Thymoma

Back 701

-Neoplasm of Epithelial portion of the Thymus
-Associated with Myasthenia gravis
--progressive muscle weakness exacerbated by exercise
-Associated with exfoliative dermatitis in cats, dogs, and rabbits
-Seen in older dogs, cattle, cats, horses, ferrets, pigs, sheep and goats
-Slow-growing encapsulated tumor
-Rarely metastasize

Front 702

Thyimc Lymphosarcoma

Back 702

-Neoplasm of lymphoid component (T-cells)
-Most often seen in younger cats (FeLV) and young cattle
-Can take up a TON of space
--clinical signs relate to space-occupying effect of the mass
-Histologically will see lots and lots of T-cells

Front 703

Causes of Small lymph nodes

Back 703

-Developmental disorders
-Immunodeficiency disorders
-Lack of antigenic stimulation
-Malnutrition
-Aging
-Viral infections
--Canine Distemper, BVDV, EHV-1, Feline panleukopenia virus, FIV, Hog Cholera
-Radiation

Front 704

Causes for Enlarged Lymph nodes

Back 704

-More common than small lymph nodes
-Hyperplasia with or without drainage
-Lymphadenitis
--bacterial, viral, fungal, protozoal cause
-Metastatic neoplasia
-Primary neoplasia
-Discoloration or pigmentation is usually associated with hyperplastic reaction

Front 705

Lymphadenopathy

Back 705

-Regional or generalized enlargement of unknown or unspecified cause

Front 706

Lymph Nodes

Back 706

-Have components of 2 different systems
--monocyte-macrophage
--lymphopoietic
-Structurally divided into 3 zones
--Superficial cortex
--Deep cortex/paracortex
--Medulla
-Surveillance and immune function
-Antigen enters lymph/blood vessels and is transported to the draining lymph node
-In lymph node antigen is surrounded by macrophages and lymphocytes

Front 707

Structural divisions of the Lymph node

Back 707

1. Superficial cortex
--B-cells form immunologically active primary follicles or active secondary follicles with germinal centers
2. Deep cortex/paracortex
--T-cells
3. Medulla

Front 708

Lymphoid Hyperplasia

Back 708

-Secondary to antigenic stimulation
-Can involve many lymph nodes (systemic disease)
-Can be localized to a regional lymph node draining an inflammed area
-Proliferation of lymphoid follicles with active germinal centers
--germinal centers expand
-Produce plasma cells that secrete antibody
-Increase in T-lymphocytes in paracortical areas
-Sub-capsular space is expanded
-Will have many different cell types in a reactive process

Front 709

Acute Lymphadenitis

Back 709

-Neutrophils have "set up shop" in the lymph nodes and are not draining out
-Targeted inflammation of the lymph nodes
-Soft, hyperemic, edema
-Usually the result of a regional lymph node draining an inflammatory site

Front 710

Chronic Lymphadenitis

Back 710

-Capsule is thick, firm, and may be fibrotic

Front 711

Bacterial lymphadenitis

Back 711

-Often pyogenic
-Strep equi (equine strangles)
-Arcanobacterium pyrogenes (cattle and sheep)
-Streptococcus porcinus (porcine jowl abscess)
-Caseous lymphadenitis in sheep and goats due to Corynebacterium pseudotuberculosis
-Mycobacteriosis: focal granulomatous infammation

Front 712

Viral Lymphadenitis

Back 712

-Porcine circovirus 2
--granulomatous with basophilic inclusion bodies
--FIP

Front 713

Fungal lymphadenitis

Back 713

-Coalescing to diffuse granulomatous blastomycosis, cryptococcosis, Histoplasma

Front 714

Protozoal lymphadenitis

Back 714

-Leishmania
-Toxoplasma

Front 715

Metastatic neoplasia to the Lymph nodes

Back 715

-Carcinomas metastasize to lymph nodes
--gastric, mammary, pulmonary, squamous, etc.)
-Firm, enlarged lymph odes with loss of normal architecture
-Malignant Melanoma
-Mast cell Tumor
-Some osteosarcomas

Front 716

Lymphosarcoma

Back 716

-Diverse group of malignancies arising in lymphoid tissues
-All lymphomas are not the same, depends on which type of cell is neoplastic
--Variable treatment and diagnosis
-Need to know sub-type to effectively treat!
-Anatomic location
-Immunophenotype
-Cellular morphology
-Histologic pattern
-Biologic behavior

Front 717

Lymphosarcoma classification system

Back 717

1. Anatomic location:
-multicentric
-Mediastinal/thymic
-Cutaneous
-Misc/solitary
-Primary to marrow
2. Immunophenotype:
-B-cell, T-cell, or none
3. Cellular morphology
-cell size
-Nuclear features
-Numberof mitoses
4. Histologic pattern
-diffuse
-follicular
5. Biologic behavior
-Low-grade to high-grade

Front 718

Canine Lymphosarcoma

Back 718

-Middle-aged or older dogs
-No retroviral cause yet
-Multicentric form is most common 80-85%
--generalized lymph node enlargement
--Splenic and hepatic involvement is common with this form
--Diffuse large B-cell Lymphoma
--Peripheral T-cell Lymphoma
-Alimentary, thymic, and cutaneous forms are less common
-Hypercalcemia is usually associated with T-cell lymphosarcoma
-Can look like whatever it wants to
--will bulge on cut section

Front 719

Feline Lymphosarcoma

Back 719

-Cats do not show lymphoadenopathy
-FeLV associated lymphoma: younger cats
--mediastinal and multicentric T-lymphocyte lymphoma
--uncommon with vacination
-Alimentary lymphoma is most common form
--older cats
-Miscellaneous sites are also seen in older cats
-Hodgkin-like lymphosarcoma in cats older than 6 years
--unilateral mandibular or cervical lymph node enlargement

Front 720

Feline Intestinal Lymphosarcoma

Back 720

-Most common form of feline lymphoma
-Occurs in older cats
-Mostly B-cell population but can also see aggressive large granular lymphomas
-Small-cell lymphoma looks like inflammatory lymphocytes

Front 721

Bovine Lymphosarcoma

Back 721

1. BLV associated lymphoma
-Occurs in superficial/abdominal lymph nodes
-Retrobulbar, abomasum, heart, uterus, spleen, kidney
-cows 6-8 years old
2. non-BLV associated lymphoma
-Sporadic form, calf/juvenile form
-Generalized lymph node enlargement and widespread visceral and bone marrow involvement

Front 722

Forms of non-BLV lymphoma

Back 722

-Thymic form: in beef cattle 6-24 months old
-Cutaneous form: rare and in young cattle
-MMulticentric form: widespread symmetric lymph nodes
--also affects liver, spleen, kidneys, and maybe skeletal muscle

Front 723

Equine Lymphosarcoma

Back 723

-Multicentric
-Alimentary
-Cutaneous/subcutaneous
-Most common subtype is T-cell rich large B-cell lymphoma
--most common at all sites

Front 724

Pig Lymphosarcoma

Back 724

-Frequent tumor
-Multicentric form in lymph nodes, spleen, liver, kidney, and bone marrow
-Mediastinal form affects pigs less than 1 year old

Front 725

Ferrett Lymphosarcoma

Back 725

-Diffuse peripheral lymphadenopathy with visceral spread late in the course of the disease
--Spreads to spleen, liver, kidney
-Juvenile form affects large lymphocytes in the thymus, spleen, and liver
--can lead to compressiong of the lung lobes, dyspnea, and pleural effusion
-Immunoblastic/polymorphous form is uncommon
--peripheral lymphadenopathy and visceral distribution

Front 726

Histiocytic Sarcoma

Back 726

-Macrophage neoplasm, affects dendritic Antigen Presenting Cells
-Common in Bernese mountain dogs, rotweillers, goldens, flat-coated retrievers
-Sporadically occurs in other dog breeds and cats
-Can be localized or disseminated
-Localized: spleen, lymph node, lung, bone marrow, skin, and subcutis are affected
-Disseminated: secondary sites throughout the body
--liver, lung, hilar lymph node, bone marrow

Front 727

Discoloration/Pigment of Lymph Nodes

Back 727

-Drainage reaction: macrophages are in medullary subcapsular sinuses with RBCs, hemosiderosis, and edema
-Anthracosis can cause carbon from the lungs to drain into tracheobronchial lymph nodes
-Melanin accumulation from chronic dermatitis or mandibular melanosis
-Parasitic hematin with Fasciola magna or Fasciola hepatica

Front 728

Spleen Structure

Back 728

-Smooth Muscle
-Afferent and efferent blood vessels
-Red and white pulp
-3 anatomic systems:
--monocyte-macrophage system
--lymphopoietic system
--Vasculature

Front 729

Spleen Red Pulp

Back 729

-Meshwork of reticular cells interspersed with macrophages
-RBCs from terminal arterioles enter red pulp and traverse sinuses or meshwork, then enter terminal venules
-Macrophages survey RBCs and trap antigenic material from plasma
-Remove foreign material, microorganisms, senescent and altered RBCs
-Store mature RBCs in red pulp vascular spaces
-Hematopoietic role

Front 730

Spleen White pulp

Back 730

-Lymphocytes and macrophages
-Surround central arterioles, form Periarteriolar lymphoid sheaths (PALS) and lymphoid follicles of B-cells
-Respond to an innumological demand by producing B lymphocytes and plasma cells
--produce antibody and memory lymphocytes

Front 731

Splenomegaly
Bloody Spleen

Back 731

-Uniformly bloody spleen
-Congestion due to torsion or barbituate euthanasia/anesthesia
-Acute hyperemia
--septicemia → microbes transported to the spleen → phagocytosis by macrophages, produces a big, bloody spleen
-Acute Hemolytic Anemia congests spleen
--need to remove large numbers of sequestered or parasitized altered RBCs from circulation

Front 732

Splenomegaly
Meaty Spleen

Back 732

-Uniform splenomegaly with a firm consistency
-Does not lose blood when cut
-Causes:
--bacteria/septicemia
--chronic infectious disease
--prolonged hemolytic anemia
--Diffuse lymphoid hyperplasia
--Neoplasia
--Storage material
--Extra-medullary hematopoiesis

Front 733

Septicemia as a cause for meaty spleen

Back 733

-Hyperplasia of splenic macrophages due to need to phagocytose organisms

Front 734

Chronic hemolytic diseases as cause for meaty spleen

Back 734

-Less hemolysis, no RBCs no bloody spleen
-May be concurrent with lymphocyte hyperplasia

Front 735

Diffuse Granulomatous disease as cause for Meaty spleen

Back 735

-Intracellular facultative pathogens of macrophages
--Mycobacterium bovis
--tubervulosis
--Brucella
--Francisella tularensis
-Systemic mycoses
--blastomyces dermatitidis
--Histoplasma capsulatum
--Leishmania
-Some fungi may also produce nodular enlarged spleens with formation of granulomas

Front 736

Follicular Lymphoid Hyperplasia in the Spleen

Back 736

-May chronic diseases induce an immune response resulting in follicular lymphoid hyperplasia
-Results in "meaty spleen"
-Lymphoid follicles are hyperplastic

Front 737

Neoplasms and Meaty Spleen

Back 737

-Lymphoma
-Mast cell tumor/mastocytosis
-Multiple myeloma
-Lymphoproliferative disease

Front 738

Stored material causing meaty spleen

Back 738

-Lysosomal storage diseases
-Amyloid

Front 739

Extramedullary hematopoiesis
EMH

Back 739

-Hormonal or physiological mechanisms signal synthesis of progenitor cells for systemic circulation
-Splenic EMH is often incidental
-Can cause meaty spleen

Front 740

Splenic Nodules with Bloody Consistency

Back 740

1. Hematoma
2. Hematoma induced by nodular lymphoid hyperplasia
--blood pools and grows into a hematoma
3. Hemangiosarcoma

All look the same

Front 741

Splenic Nodules with a Firm consistency

Back 741

1. Focal nodular lymphoid follicular hyperplasia
2. Granuloma (mycobacterium)
3. Abscesses
--strep
--rhodococcus
--arcanobacterium
--corynebacterium
4. Neoplasms

Front 742

Neoplasia causing form splenic nodules

Back 742

Primary:
-Lymphoma
-Histiocytic sarcoma
-Fibrohistiocytic nodules/complex nodular hyperplasia
-Leiomyosarcoma
-fibrosarcoma
-undifferentiated sarcomas
Metastatic sarcomas and carcinomas can seed in the spleen

Front 743

Primary tumors in the Spleen

Back 743

1. Leiomyosarcoma
2. Fibrosarcoma
3. Lymphosarcoma

Front 744

Small Spleens

Back 744

-Hypoplasia and atrophy
-Not common
-Developmental cause: immunodeficiency diseases
-Atrophy due to aging or wasting diseases
-Contraction of the spleen

Front 745

Splenic Choristoma

Back 745

-Benign nodular hyperplasia of the spleen
-If developmental, presence of normal tissue at an abnormal site
--"daughter spleens"
-Can also be acquired through traumatic splenic rupture
--splenosis

Front 746

Siderofibrotic plaques on the spleen

Back 746

-Gray/tan plaques on splenic capsule
-Accumulation of Iron/hematoiden and calcium
-Common incidental finding in aged dogs
-Usually occur along the marginal surface of the spleen

Front 747

Splenic Infarct

Back 747

-Wedge-shaped regions of spleen
-red/black in color are acute
-tan are chronic

Front 748

Pathology of the Tonsil

Back 748

1. Lymphoid depletion
--occurs with viral infections that cause immunosuppression
2. Inflammation
--only primary or hematogenous infections, no afferent lymphatics to bring stuff in
--necrotizing tonsilitis
3. Inflammatory polyps (old dogs)
4. Neoplasia
--only primary neoplasms, no afferent lymphatics
--Squamous cell carcinoma, lymphoma, melanoma

Front 749

Primary Immunodeficiency Diseases

Back 749

-Genetic causes
-Generally uncommon
-Break in somewhere maturation cascarde from stem cell to mature cell
-Lots of cross-talk in maturation process
-Severe Combined Immunodeficiency (SCID)
-Agammaglobulinemia
-Selective immunoglobulin deficiencies
-Leukocyte adhesion deficiency
-Complement deficiencies

Front 750

Severe Combined Immunodeficiency in Horses
Equine SCID

Back 750

-Autosomal recessive trait
-Expressed as an absence of functional B and T lymphocytes
-Defect in the catalytic subunit of DNA-dependent protein kinase
--enzyme is required for receptor gene rearrangements for B and T cell maturation
--no maturation of B and T cells
-About 10 days old animal develops diarrhea and pneumonia
-Adenovirus, cryptosporidium parvum, pneumocystis carinii are common pathogens
-Affected foals die before 5 months old
-Hypoplasia of the thymus, spleen, and lymph nodes

Front 751

Severe Combined Immunodeficiency in Bassett Hounds
Canine SCID

Back 751

-Mutation in gene encoding common gamma subunit of IL-2, IL-4, IL-7, IL-9, IL-15
-T-cells are unable to bind and respond to IL-2
-B-cells are unable to class switching, no IgG formed
-Animal does not grow normally and has increased susceptibility to infection
-Very small thymus with unidentifiable lymph nodes and tonsils
-X-linked (X-SCID)

Front 752

SCID in Corgis and Jack Russell Terriers

Back 752

-Autosomal recessive disorder instead of mutation
-Corgis have similar disease as bassetts
-Jack Russell's have mutation in DNA-Protein kinases similar to Arabian horses

Front 753

Acquired Immunodeficiencies

Back 753

-Much more common, occur for many more reasons
-Pregnancy, aging, malnutrition
-Toxins (PCBs, Iodine, lead, Cadmium, methylmercury, DDT)
-Drugs (corticosteroids, chemotherapeutic agents)
-FeLV
-FIV
-Parvovirus