Toxicology Block 8

Front 1

What are the causes of reproductive failure in any spp?

Back 1

infectious disease, poor nutrition, adverse weather, hormonal imbalances, stress, and exposure to toxins

Front 2

What is the progression of spermatogenesis?

Back 2

spermatogenesis takes place in the testes--> (spermatocytogenesis) spermatogonia develop into spermatocytes then develop into spermatids then develop into spermatozoa. (process of spermatids to spermatozoa is called spermiogenesis)

Front 3

What cells is testosterone derived from?

Back 3

Leydig cells (clustered epithelioid cells found in teh testicular interstitium)

Front 4

What are the seritoli cells responsible for?

Back 4

(line the semineferous tubules), synthesize numerous proteins (androgen-binding proteins and others for which a function is not known). Trophic substances (lactates, pyruvates, and alpha-keto acids that are used by spermatocytes)

Front 5

What are some of the ways that toxicants can interfere with male reproduction?

Back 5

Biotransformation: toxicants can interfere with both spermatogenesis and steroid production. However cytochrome, P450, mixed function oxidases (MFOs), and epoxide-degrading enzymes are present in low levels in the seminiferous tubules
Blood-testis barrier: prevents free access of drugs and toxicatns to the seminiferous tubules, however less developed in immature animals, and leydig cells are not part of the barrier and may be unprotected

Front 6

What are the mechanisms of toxicologic damage in regards to abortion?

Back 6

impair spermatogenesis or the physical delivery of spermatozoa to the oocyte:
inhibition of cell division or differentiation; inhibition of intermediatry metabolism; interference with androgen production

Front 7

How can toxicants affect the normal ovarian function?

Back 7

impaired gonadotropin secretion interrupts the trophic and cyclic influences on normal ovarian function: food deprivation or starvation (reduces energy levels, inhibits secretion of gonadotropins); stress (leads to increased epinephrine which stimulates corticosteroid secretion, leading to reduced LH secretion); estrogens or estrogenic toxicants impair gonadotropin release and inhibit activity of the ovary
impaired follicular development: when toxicants damage the oocyte or interfere with the ability of follicular (granulosa) cells to proliferate.

Front 8

What toxins can interfere with implantation?

Back 8

zearalenone mycotoxins and other estrogens: interrupt the necessary secretory responses that normally occur in teh fallopian tubes and uterus just prior to implantation
high protein diets for dairy cows: associated with reduced viability of fertilized embryos, apparently as a result of elevated ammonia levels in blood and uterine secretions

Front 9

What are some of the causes of an extension of the postpartum interval?

Back 9

abortion, extended lactation time, inadequate nutrition during lactation, ingestion of toxic plants (Veratrum californicum by sheep and Lupinus spp by cattle), zearalenone mycotoxin (and other estrogens in swine), recombinant bovine somatotropin (rBST), has been associated with an increased postpartum nonpregnant peroid ("days open") in dairy cows with high milk production stimulated by rBST), and Hormonal implants, plant estrogens and estrus-synchronizing agents.

Front 10

What is the clinical sign noted when toxicants cause fetal death in the first trimester?

Back 10

delayed return to estrus and fetal resorption

Front 11

What is the clinical sign noted when toxicants cause fetal death in the second trimester?

Back 11

mummification; some or all of the liter may be affected, occurs after the beginning of skeletal calcification

Front 12

What are the toxins known to cause mummification?

Back 12

few toxic causes are known, but mycotoxins such as zearalenone, ochratoxin, and trichothecenes are associated with increased mummification rates in swine

Front 13

What is the clinical sign noted when toxicants cause fetal death in the third trimester?

Back 13

abortion (expulsion of recognizable fetus)
cause of many abortions is unknown

Front 14

What are some abortificant toxins (third trimester)?

Back 14

heavy metals, and poisonous plants

Front 15

What are the clinical signs associated with carboxyhemoglobinemia?

Back 15

cherry-red color of the skin and mucous membranes in carbon monoxide poisoning results from the color of carboxyhemoglobin, not oxyhemoglobin.
fetal anoxia, leading to near-term abortions and stillbirths

Front 16

What is the mechanism of toxicity of carboxyhemoglobinemia?

Back 16

no intrinsic mechanism to distinquish oxygen from carbon monoxide; carbon monoxide competes reversibly with oxygen for ferrous heme binding. The affinity of CO for hemoglobin is 240 times that of oxygen

Front 17

What are the effects of Astragalus (locoweed) during mid-to late pregnancy?

Back 17

Commonly causes abortion. Teratogenic effects (ie. contracted tendon) and reduced spermatogenesis leading to male infertility also occurs

Front 18

What is the toxic effect of Iva augustilfolia (sumpweed)?

Back 18

affected by plants in the seedling stage; causes abortions in the last half of the gestation period, following several weeks of consumption by the pregnant cow

Front 19

What are the effects of Pinus ponderosa (western yellow pine, ponderosa pine)?

Back 19

(the evergreens)unidentified, water-soluble agent in fresh and dried pine needles causes abortion in cattle: another resource said ICA: isocupressic acid?

Front 20

What is the clinical presentation of the pinus ponderosa plant?

Back 20

aboriton is common in the last trimester of pregnancy and is often accompanied by edema of the udder and vulva in the dam; retained placentas and metritis often are part of "pine needle abortion syndrome"

Front 21

What is the toxic principle of xanthocephalum (western broomweed)?

Back 21

it is considered to be a saponin

Front 22

What are the clinical signs of xanthocephalum?

Back 22

actue toxicosis: depression, anorexia, nasal discharge, and diarrhea
chronic toxicosis: first two-thirds of gestation, calves are small (aborted), and retained placentas.

Front 23

What are the estrogenic plants?

Back 23

Trifolium repens (high estrogen clover); T. subterraneum (high content); Medicago sativa (alfalfa)(weakly to moderately estrogenic)

Front 24

What is the toxic principle of estrogenic plants?

Back 24

isoflavone estrogens, genistein, and formononetin, are responsible for causing clincial estrogenism associated with Trifolium. Formononetin is non-estrogenic but is metabolized to an estrogenic compound, equol.

Front 25

What is the mechanism of toxicitiy with estrogenic plants?

Back 25

excessive levels of estrogen interferes with transport and fertility of ova, cause cystic hyperplasia of the cervix, and induce feminization and reduced libido in males

Front 26

What is the toxic principle of Pines?

Back 26

isocupressic acid (ICA) (labdane resin acid)

Front 27

What is the mechanism of the toxic principle of pines?

Back 27

causes a marked constriction of the caruncular arterial bed and increased uterine tone causing premature parturition hence weak calves are born

Front 28

What is the toxin and clinical result of poison hemlock?

Back 28

crooked calf disease aka multiple congental contracutres (MCC); The toxin is Coniine

Front 29

What is the mechanism of the toxic principle of Locoweed (Astragalus)?

Back 29

affects the CL, chorioallantois, cardiac myocytes and neurons, abortions (occurs at any stage) and deformities are also common; chronic condition, ingestion must occur for 4-6 weeks
males: spermatogenesis is greatly reduced possibly attributable to hypertensive effects or vacuolation of the glandular tissue

Front 30

What is the toxin associated with Broomweed (Guttierrezia microcephala)?

Back 30

aka snakeweeds
mono and diterpenes, saponins, and oxygenated falvonol methyl esters

Front 31

What is the toxin associated with Lupines?

Back 31

anagyrine (alkaloid), ammodendrine

Front 32

What are the toxic effects of Lupines?

Back 32

MCC's (multiple congenital contractures); including arthrogryposis, torticollis, kyphosis, scoliosis

Front 33

What are the toxic effects associated with mycotoxins?

Back 33

especially common on fescue grass, reproductive inefficiency rather than abortion; zearalenone (cattle are relatively resistant)

Front 34

What are the toxic effects of nitrates/nitrites?

Back 34

found in fertilizers; nitrate reducing rumen microbes increase susceptibility, methmoglobinemia is a common complication, late term aboritons due to hypoxemia of fetus

Front 35

What are some common renal toxins that affect animals?

Back 35

grapes and raisins
cattle: oak and acorns
Ethylene glycol
aminoglycosides

Front 36

What is the toxin assoicated with oaks and acorns?

Back 36

tannons

Front 37

What are the effects of ethylene glycol?

Back 37

end result is calcium oxalate crystals that block the tubules causing tubular nephritis; alcohol-->alcohol dehydratodenase-->glycolic acid which leads to metabolic acidosis--> systemic signs
glycolic acid-->asillic acid--> forms with calcium causing calcium oxalate int eh brain and kidney mainly
Renal failure results in 2-3 days

Front 38

What plant in large animals leads to the destruction of spermatognoia?

Back 38

gossypol/cottonseed (monogastric animals more likely to see cardiac signs with gossypol)

Front 39

What does amiraz cause?

Back 39

causes CNS toxicity, kids can die from licking it

Front 40

Functional Magnetic Resonance Imaging (FMRI)

Back 40

A technique for revealing blood flow and, therefore, brain activity

Hint 40

A technique for revealing blood flow and, therefore, brain activity by comparing successive MRI scans. MRI scans show brain anatomy; these scans show brain function.

Front 41

How does colchicine toxicity present?

Back 41

vomiting and diarrhea early overdose signs
bloody diarrhea, paralytic ileus, renal failure, hepatotoxicity, pancytopenia, paralysis, shock, vascular collapse

Front 42

What is the treatment for colchicine toxicity?

Back 42

no antidote
GI removal: charcoal, emetics, laxatives
Extensive GI recycling will need repeated!

Front 43

Where is colchicine extracted?

Back 43

crocus plant "meadow saffron

Front 44

How does aminoglycosides cause renal toxicity?

Back 44

cause polycationic properties
polycations bind negative-charged proximal tubule endothelim--> pinocytosed--> disrupts cell function--> acute tubular necrosis
competitive antagonist of nicotinic Ach receptors (respiratory paralysis,ect.)

Front 45

What are the three stages of ethylene glycol overdose?

Back 45

excitation within first few hours-->CNS depression (alcohol)
metabolic acidcosis (due mostly to glycolic acid accum.)
Delayed renal insufficiency from deposition of oxalate crystals in renal tubules

Front 46

What is the treatment for ethylene glycol toxicity?

Back 46

fomepizole, IV or ethanol
inhibits alcohol dehydrogenase and decreases concentrations of toxic metabolites

Front 47

How do NSAIDS cause renal toxicity?

Back 47

inhibits prostaglandin synthesis--> inability to dilate afferent arteriole--> decreased renal perfusion--> renal ischemia
HORSES MOST SUSCEPTIBLE!!!

Front 48

What are the effects of raisin toxicity?

Back 48

MOA is unknown but causes renal tubular necrosis
may see golden-brown pigment in renal epithelial cells

Front 49

How do tannins' cause toxicity?

Back 49

metal ion chelators- binds and prevents mineral absorption in GI lumen (iron--> anemia)
precipitates protein- decreases nutrient availability in ruminants (high feed of sorghum)
reduces bioavailablilty of plant-derived iron (non-heme)- no effect on animal-derived iron (heme) absorption
*may be renal protective*

Front 50

In what plant is gossypol found?

Back 50

cottonseed (yellow pigment)

Front 51

What is the mechanism behind gossypol?

Back 51

male infertility MOA is unknown but it is a polyphenolic aldehyde which inhibits dehydrogenases
destroys cardiac muscle, binds calmodulin, inhibits protein kinase c

Front 52

What is the MOA of zearalenone toxicity in regards to reproduction?

Back 52

Mycotoxin Fusarium sp. is estrogenic and causes negative feedback on pituitary--> decrease in FSH--> inhibition of ovarian follicle maturation and ovulation; usually from corn and affects pigs more so than cows

Front 53

What is the MOA of nitrate accumulators in regards to reproduction?

Back 53

in rumen, nitrate--> nitrite--> NH3
Nitrities build up and enter bloodstream-->oxidizes Fe2+--> Fe3+ (methmeglobin)
methmeglobin cannot carry O2
animal will become anoxic
will lead to abortion and death

Front 54

How do phytoestrogens affect reproduction?

Back 54

bind estrogen-->interfere with transport and fertililty of ova--> cystic hyperplasia of cervix--> infertility
feminizes males
males: induces loss of libido

Front 55

What is the MOA of amitraz toxicity?

Back 55

alpha 2 agonist activity in CNS--> sedation
inhibits monamine oxidase and anti-serotonin--> CNS depression

Front 56

What are the OD signs of amitraz?

Back 56

vomiting, depressoiin, disorientation, ataxia, bradycardia, coma, seizures

Front 57

What are the clinical signs of organophosphate/carbamate toxicities?

Back 57

cholinergic: salivation, lacrimation, miosis, urination, dyspnea (bronchial secretions, constriction), defication, colic, muscle fasiculations, tremors, tachycardia, depression or stimulation, and convulsions

Front 58

What is the MOA of OP/carbamate toxicity?

Back 58

OPs: binds to serine hydroxyl group of hte esteratic site of the Ach-ase enzyme. agent is partially hydrolyzed creating a stronger bond between the compound and the enzyme (irreversible)
Ach is not hydrolyzed at the synaptic cleft, increasing the stimulation of receptors
Carbomates: binding and inhbitory actions are similar to those of OPs. After hydrolysis of compound, Ach-ase undergoes carbamoylation. are poor substrates for Ach-ase, and spontaneous reactivation of enzyme is rapid

Front 59

What is the MOA of selenium toxicity?

Back 59

can act as an oxidant that causes oxidative stress; decreased gluathione peroxidase activity, increased lipid peroxidation, can interfre with sulfhydryl groups, displacement of sulfur or sulfur aa

Front 60

What are two main toxins that cause smacking of lips?

Back 60

batteries, and pyrethrins

Front 61

What are some potential pyrexia causing toxins of cattle?

Back 61

blister beetles, pine oil, hops, pyrethrins, black walnut, ergot, snail bait (metal aldehyde)

Front 62

What are some potential toxins that cause drooling/salivation in cattle?

Back 62

OP, carbamates, ergot, oleander, alkaloids, blister beetels, etc.

Front 63

What are the top toxins causing bruxisim in cattle?

Back 63

cicutoxin, quinolizidine alkaloids, oxalates, alsike clover, red clover, fluoroacetate

Front 64

What are some toxins causing lameness in cattle?

Back 64

blister beetles, ergot, fluoroquinolones, fluoride, molybdenum, selenium, zinc, vitamin A, etc.

Front 65

What are the top toxins causing stamping of feet?

Back 65

OP's and carbamates

Front 66

What are some toxins that cause nasal discharge?

Back 66

stachbotryotoxin (mold), iodine, ionophores, ammonia, phenols, pyridine alkaloids, gutierrezia (broomweeds), Ligustrup spp (olive tree family)

Front 67

What are some toxins causing vesicles/blisters?

Back 67

terpene, blister beetles, brown recluse spider, fluoroquinolones, paraquat, protoanemonin

Front 68

What is the MOA of toxicologic damage of pyrethrins?

Back 68

pyrethrins act on sodium channels in the axonal membrane, decreasing and slowing inward sodium conductance and suppressing potassium outflow. they may also inhibit adenosine triphosphate (ATPases), which may affect cation conduction at axonal membranes. The net result is decreased action potential amplitude and the generation of repetitive nerve impulses.

Front 69

What is the toxic principle of blister beetles?

Back 69

canthardidin, strongly irritating to mucous membranes, the GI mucosa, and UT. may lead to hypocalcemia in heavy exposure with an unknonw mechanism

Front 70

What is the toxic principles of the brown recluse spider?

Back 70

the toxin consists of at least eight proteins, including hyaluronidase, proteases, other spreading factors, and hemolysins. The mechanism of action is not well defined, but the toxin damages endothelial cell membranes, leading to intravascular coagulation, capillary thrombi, and tissue necrosis

Front 71

Where are the highly permeable areas of integument for chemical absorption (toxins)?

Back 71

axillary, inguinal, mammary, and scrotal skin
birds is the skin on their feet

Front 72

What are the effects of dermal hyperemia?

Back 72

increases in environmental temperature may enhance absorption of chemicals
ie. hot climates dermal hyperemia may increase the toxicity of OP's to cattle

Front 73

What types of toxicants effect the integument?

Back 73

highly lipophilic substances or substances that contain surfactants or detergents

Front 74

What layer of the skin has the ability of biotransformation of xenobiotics?

Back 74

Deep layers of the epidermis!
Dermis has NO significant xenobiotic metabolizing activity.

Front 75

What is the repsonse to integument toxicants?

Back 75

irritation, degeneration, and necrosis (elicits an inflammatory repsonse; ie. acids, alkalies, some metal salts, generally pH of less than 2 or greater than 12)
allergic contact dermatitis: chemicals that act as antigens by combining with a carrier protein, eliciting a response from cellular components of the immune system; Langerhan's in the epidermis process the antigen and interact with the T lymphocytes to form a sensitized T lymphocytes
Photosensitization: an increase in susceptibility to ultraviolet light, free radicals produced by photodynamic reactions can damage cell and lysosomal membranes

Front 76

What are the conditions that lead to photosensitization?

Back 76

depends on the absorption of ultraviolet light within a specific range of wavelengths (280-790 nm) and the presence of photodynamic agent in the skin
photosensitization is most prominent on areas of the body where protection from sunlight is least effective
most likely to occur in sunny climates and during the spring and summer when sunlight is more intense or of longer duration each day

Front 77

What are the clinical effects of photosensitization?

Back 77

early signs are erythema and edema
pruritus, photophobia, and hyperesthesia
exudation ("weeping") of serum, formation of vesicles, ulceration, exfoliation of damged epidermis, and possibly blindness

Front 78

What are the different types of photosensitization?

Back 78

primary: occurs when photodynamic agent is directly ingested, absorbed through the skin, or injected or when a chemical is biotransformed to a photodynamic metabolite
secondary: occurs as a result of compromised liver function, which reduces the excretion of plant pigment metabolites from the body. several toxic plants are known to cause hepatogenous or secondary photosensitization
trauma: plants causing physical injury to mm etc.
hyperkeratosis: highly chlorinated naphthalenes and hairy vetch (vicia villosa) are toxicants that cause this
alopecia: associated with thallium, arsenic, and selenium toxicosis, chemotherapy, and consumption of the leucaena plant
carcinogenesis: skin cancer is usually not closely assoicated with chemical exposure in animals