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164 Cards in this Set

  • Front
  • Back
Pathophys of hypoxia--go.
Leads to decreased ox phos --> decr ATP. Body tries to form ATP from glycogen (anaerobic resp) --> lactatemia
When we talk about membrane damage and increased membrane permability we are talking about toxins that bind to ______ groups in the membrane proteins
--SH
Free radical production results in what 3 things?
Lipid peroxidation
Protein damage
DNA damage
Whats the difference between acute & subacute exposure?
Acute is single or repeated exposure over 24 hours while subacute is exposure over 1-30 days

(same goes for acute/subacute responses)
Cyanides and organophosphates result in acute, subacute, or chronic exposure and reaponses?
Acute exposure and response
What are two toxicities that result in acute responses from chronic exposures?
Lead & Cu in sheep
Fluorosis and lead toxicity causing debilitation are examples of what kind of exposure and response?
Chronic
When free radicals combine with PUFAs, lipid peroxidation results in lipid peroxyl radicals.

What effect does this have on cells?
Membrane injury and cell death
With decreased ATP production comes decreased Na/K ATPase activity.

What effect does this have on the cell?
Influx of water and cell swelling
Free radical production leads to lipid peroxidation.

Name two prime examples of free rads.
Singlet oxygen & hydroxyl groups

Idk if i know what im talking about
Name two effects of increased intracellular Ca?
Phosholipases kill the phospholipid membrane

Proteases are also activated
Ionizing radiation can lead to what 2 free radicals?
Hydroxyl free rads & hydrogen free rads
Metabolism of some chemicals produces what 2 radicals?
Superoxide and hydroxyl radicals
So radicals cause lipid peroxidation, protein damage, and DNA damage.

T/F. The resulting peroxides are reactive and cause further damage.
False
How do radicals cause protein damage?
Free rads oxidize amino acids
How do radicals damage DNA?
By reacting with thymidine to break the strands
Name four antioxidants
Vit E,A,C, GSH
What do antioxidants do?
Scavenge radicals and reduce their formation
Name three enzymes that scavenge free radicals and destroy oxidants.
Catalase, superoxide dismutase, glutathione peroxidase
Describe the valence of oxygen free radicals?
Oxygen with unpaired electron, is usually short-lived and highly reactive
Equations--eek!
Yeah i dont get simple chemistry
The threat of oxidative stress arises from what 3 things?
Superoxide free radical, hydrogen peroxide, hydroxyl free radical
Whats GSH reductase doing?
Converting GSSG to GSH, an antioxidant
Whats GSH peroxidase doing?
Converting hydrogen peroxide to water
What are flavonoids
Plant pigments
What are the four groups of flavonoids?
Flavones
Flavonones
Catechins
Anthocycanins
What do we use flavonoids for?
As antioxidants and free radical absorbers

(they can also inhibit WBC degranulation & inhibit pgospholipase A2 & therefore PGs and leukotrienes from being formed)
What IS oxidative phosphorylation?
ADP --> ATP & water (requires electrons and H+)
What is a cytochrome?
Iron-containing protein with a heme group
What is an uncoupler of oxphos we have larned about?
Inorganic Arsenics
What does uncoupling of oxphos mean?
They dissociate oxidation from phosphoeylation--ie oxygen is still utilized but the energy becomes heat instead of ATP (instead of going into forming another phosphate bond)
Why are toxicants delivered to the cortex in higher quantities than the medulla?
Because the cortex receives 90% of blood flow
Because of the renal countercurrent system, despite higher quantities of toxin going to the cortex, higher ______ may reach the medulla
Concentrations
The loop of ahenle increases tonicity of "urine". What is the relevance to toxicology?
Higher & higher concentrations will reach the DCT then collecting duct than had originally been delivered to the PCT
Where can the kidney transform prodrugs to their toxic forms?
In the PCT because she xontains cytochrome P450
Cats are deficient in ________, leading to acetaminophen toxicity.
Glucuronyl transferase
How is acetaminophen ezcreted?
As glucuronide
What might explain the blood-related signs we see with acetaminophen toxicity?
RBC glutathione is overwhelmed, allowing excess acetaminophen to react with SH groups in Hb.
What is paracetamol?
Acetaminophen
CS of a cat with acetaminophen toxicity?
Cyanosis, dyspnea (shallow breaths), facial and paw edema, icterus & chocolate urine, hypothermia
Treatment fkr acetaminophen toxicity?

Why?
Mucomyst (N-acetyl cysteine) .... It forms cysteine, which is a sulfur souce that causes glutathione synthesis
Whats the differnece between potosens and sunburn?
Different wavelengths (photosens longerz)
Whats the deal with photosens?
Light energy --> chemical energy --> free rads (superoxide) --> membrane damage
What are the three types of photosens?
Congen, primary, secondary
Whats congenital photosens due to?
Heme synthe disturbances --> porphyrin accumulations
Prumary photosens?
Eg hypericin (board Q)...ingestion of this compound directly causes photosens
Secondary photosens?
Excretory disturbance (liver dz or posthepatic obstruction) --> accum of photochemicals
CS of photosens
Erythema and edema
Serous oozing
Necrosis and sloughing of skin (esp white skin in cattle)
Whats your commonest signalment for lead toxicity?
Think calves & young dogs
Most ingested lead is absorbed or excreted in the feces?
Excreted in feces, only 2-10% is absorbed in adults
In adults, only 2-10% of ingested lead is absorbed. Is this the case for neonates?
No, neonates absorb 50% of ingested lead.
Who absorbs more ingested lead--cows or dogs?
Dogs (monogastrics)
So sum up lead absorption
Neonates > adults
Monogastrics > R
So some lead has been absorbed. Where is it in the blood?

Is the a lot of free lead in the blood?
Almost all of it is in the RBCs as its proteinate or phosphate form. A very small % is in the plasma bound to albumin.

There is almost no free lead in the blood.
What enhances lead absorption?
Vit D
So once lead has been absorbed and transported via the RBCs, what organs does it set up shop in?
Bone >> kidney, liver
The majority of ingested lead is excreted in the feces. What is the ultimate fate of absorbed lead?
Slowly excreted in the urine, feces, milk
What is the effect of lead on a fetus?
If the mom has lead in her system it can cross the placenta & the fetus' BBB --> teratogenic effects --> abortion or stillbirth
Is excretion of absorbed lead fast or slow?
Very slow
What does Pb2+ replace in the bones?
Ca2+
Heme synthetase has a ______ group that lead interferes with.
SH
Whixh enzyme is most sensitive to lead toxicity & therefore will be found in decreased amounts in an affected animal?
ALA dehydrase
With lead toxicity you find large amounts of ALA in the ____
Urine.
Lead toxicity will result in what changes on CBC & blood smear?
Anemia
Basophilic stippling
T/F. Lead toxicity depresses the bone marrow.
True
Why does lead toxicity lead to cell death?
Lysosomes rupture --> releaee of acid phosphatase. This enzyme is required for cell energy production, so without it the cell will die.
What is the effect of lead toxixity on the nervous system?
Decreased blood supply & energy
Leaky capillries
--> Cerebral edema & blindnes

PNS demyelination

(also fucks with GABA, NMDA, serotonin)
Lead tox --> decreased absorption of ______
Se
You have 3 bovine patients affected with lead toxicity. An adult with acute toxicity, an adult with subacute toxicity, and a calf with acute toxcity.

Which one will probably die first?
Idk i think the calf is more severe
Describe acute lead toxicity in a calf.
Since its a baby its going to absorb a lot more of the ingested lead than his mom will.

His nervous system will be affected--demyelination--> larpar --> drooling/coughing/dyspnea (makes sense); hyperesthesia (dont touch me!), tetany, convulsionsseizuredeath
Peracute caees of lead toxicity in cattle can result in sudden death. Lets say she ate the car batteries a couple days ago. What might be a sign of lead tox?
Blindness & head pressing
(muscle fasciculations & ataxia too...its a neuro thing)
Chronic lead toxicity in dogs results in wasting. Does this happen to cattle?
No wasting in cattle
Subacute lead toxicity can lead to colic in cows (most Things dont really make cows colic). What are signs of pain in a cow?

What are some of the GI issues shell have going on?
Bruxism (teeth grinding)

Constipation followed by smelly diarrhea. Ruminal stasis.
Why might lead toxicity cause roaring (dysphonia) in horses?
Nerve demyelination
Name some signs of lead toxicity in horses.
Anorexia, roaring, knuckling of fetlocks --> limb paralysis
You have 3 bovine patients affected with lead toxicity. An adult with acute toxicity, an adult with subacute toxicity, and a calf with acute toxcity.

Which one will probably die first?
Idk i think the calf is more severe
Describe acute lead toxicity in a calf.
Since its a baby its going to absorb a lot more of the ingested lead than his mom will.

His nervous system will be affected--demyelination--> larpar --> drooling/coughing/dyspnea (makes sense); hyperesthesia (dont touch me!), tetany, convulsionsseizuredeath
Peracute caees of lead toxicity in cattle can result in sudden death. Lets say she ate the car batteries a couple days ago. What might be a sign of lead tox?
Blindness & head pressing
(muscle fasciculations & ataxia too...its a neuro thing)
Chronic lead toxicity in dogs results in wasting. Does this happen to cattle?
No wasting in cattle
Subacute lead toxicity can lead to colic in cows (most Things dont really make cows colic). What are signs of pain in a cow?

What are some of the GI issues shell have going on?
Bruxism (teeth grinding)

Constipation followed by smelly diarrhea. Ruminal stasis.
Why might lead toxicity cause roaring (dysphonia) in horses?
Nerve demyelination
Name some signs of lead toxicity in horses.
Anorexia, roaring, knuckling of fetlocks --> limb paralysis
What body system is affected by lead toxicity in horses?
PNS
You are presented with a cachexic dog. His abdomen is painful on palpation and he has a history of trying to eat but not being able to swallow? What do you suspect and what might you see in his urine?
Lead toxicity.

Glucose
T/F. Lead toxicity affects the kidneys
True (at least in dogs it def does)
Nucleated RBCs are seen in a dog without anemia. What might he have?
Lead toxicity.

More often you see basophilic stippling and regen anemia (aniso, polychromasia, poikilo)
What two toxicites can cause polioencephalomalacia?

Which can cause poliomyelomalacia?
PEM <-- lead or sukfur

PM <-- se (subacute neuro form)
What two toxicities give centrilobar degeneration of the liver?
Lead and zinc
T/F. You might see porphyrins in the urine of an animal with lead toxicity.
True
T/F. Lead causes radiopacity of long bones around the epiphyses.
Sure, but its not diagnostic
T/F. Decreased ALA dehydrase is diagnostic for lead toxicity.
False? Its just a screeing test, not a diagnostic test? Thats what i wrote i class who knows
ALA dehydrase is an enzyme of what cell?
RBCs
Which of the following tests is most sensitive for lead toxicity?

Urinary lead
Urinary ALA
blood ALA
ALA dehydrase
Hair lead
ALA dehydrase....ie changes will show before any of the other tests would pick up on lead tox
With lead toxicity, do you have to decontaminate the stomach (ie with emetics)?
No, cause this animal wouls have eaten it a week ago or so
Chelation therapy for lead =
EDTA
How is EDTA given for lead toxicity?
Only by injection, never orally
How does EDTA work?
It chelates the lead from bone for redistribution of the lead (EDTA has a calcium on it, but has a higher affinity for lead. Thats how it grabs onto the lead to take it out of the body)
Whats a complexing treatment for lead toxicity?
DMSA* or dimercapeol (BAL)
T/F. DMSA is less toxic than BAL and can be given orally
True
Do we use D-penicillamine for lead toxicity?
No. We do use it for Cu toxicity in Bedlingtons tho
What is supportive therapy for lead toxicity?
Initiate urine flow & give mannitol + CCS for cerebral edema. Possibly enemas
T/F. All inorganic arsenic compounds are toxic.
True
Trivalent arsenic _______, pentavalent = _______
TrI = arsenIte

PentA = arsenAte
How do animals get arsenic?
Feed
Which valency is more toxic and whya.
Arsenite (3+) because it is more rapidly absorbed.
95% of absorbed arsenic is associatd with
RBCs
Where does arsenic accumulate before redistribution?
Liver, then is redistributed to a shit ton of other plces
Where is arsenic stored?
Bones teeth hair hoof skin (think keratin)

Liver, kidney
Why is arsenic stored in places like hoof and hair?
Because it reacts with/binds to idk the --SH grops in keratin
What is the rate of excretion of arsenic?
Rapidly excreted thru urine, feces, sweat, and milk

(sweats a new one)
Which vakenxy accumulates in tissues, and which is rapidly excreted in the urine?
Trivalents accumulate (theyre the toxic ones) and pentavalents are rapidly peed out
With inorganic arsenic compounds, poisoning is ______ or _______.
Acute or subacute
Trivalent salts are ______ to pentavalents for excretion in:

Pentavalents are reduced to trivalents by the kidney (dumb kidney!)
Oxidized; bile
Whats the MOA of trivalent arenites?
They act with --SH groups in cellular enzyme systems eg The citric acid cycle
Whats the MOA of arsenates (pentavalents)?
Uncouple oxphos --> depleted cell energy (but NO heat depletion unlike other uncouplers)
Arsenic affects tissues rich in oxidative systems. List them (6)
Rapidly dividing tissues like GIT
kidney
Liver
Lungs
Skin
Splanchnic capillaru beds
What does arsenic poisoning lead to?
Hypovolemic shock
GIT edema & shit
Nephrosis
Arsenic results in what CS
Watery --> Bloody diarrhea (peracute--> subacute)
Is chronic arsenic poisoning common?
No because its so rapidly excreted
What are the two important PM findings in arsenic poisoning?
Garlic breath & vivid red gut
Arsenic results in primarily GIT or CNS signs?
GI
Gutzeits & Reinsch tests are for what toxicity?
Arsenic

(Gutzeit is for urine)
T/F. Arsenics cause GI & shock, while lead causes more CNS signs.
True
Treatment for arsenical poisoning?
DMSA* & sodium thiosulfate
Whats the treatment for arsenicals & mercury?
DMSA & sodium thiosulfate
Hat is Succimer?
DMSA
Organoarsenicals...what so you think?
PPP (pig, poultry, PNS)
The organoarsenicals have what valency?
They are pentavalent 5+
T/F. Organoarsenials have a wide saftey margin, so high doses are needed to create toxicity.
True, usually do to feed miscalculations!
T/F. Organoarsenical toxicity usally results in low morbidity but high mortality.
False. Organoarsenicals have high morbidity but LOW MORTALITY (its not gonna kill them that much)
Lets talks cows.
Yes, lets.
Whats gonna cause a cow with lameness and tooth issues?
Fluorosis
Whats gonna cause spontaneous fractures in a cow?
Fluorosis
What causes PEM in cows?

(polioencephalomalacia)
Sulfur
In addition to PEM, what will you find on necropsy of a cow with sulfur toxicity?
Dark thick ruminal fluid (ew)
Spectacles =
Mo toxicity
Mo toxicity causes a lot of "s" CS. What are they?
Spectacles
Smelly green Scours (diarrhea)
oSteoporoSiS
exoStoSeS
rickettS
Sanemia (ok just anemia)
What causes CNS signs in cattle--organic or inorganic Hg?
Organic
What is the cause of "alkali disease"?
Selenium toxicity
What are the signs of Se toxicity in cattlw?
They lose their switch (aka tail hair)
Their claws become deformed
Dull coat

....its all about the keratin
Ok that was an incomplete card. What else do you see with Se toxicity in cows?
Emaciation
cold Extremities
Arthritis & anemia
What two toxicities can cause a blind cow?
Lead and organic mercury
What can cause acute nephritisa.
Inorganic mercury....it causes more GI signs in cows tha organic mercuries
What causes hemolytic anemia?
Zn
CS of Zn toxicity in cows?
GI shit, weight loss, hemolytic anemia, PUPD, paresis, exophthalmos
Which three toxicities affect cow eyes?
Lead, organic mercury (blindness)
Zn (exophthalmos)
Whixh toxicity causea depression in adult cattle but excitement in calves?

(and therefore affects the CNS)?
Organic mercurials
If someone broke a thermometer in a cows mouth, what would the mercury do?
Leave a silvery gray black line on the gums of course

(no im not that dumb but thats a good way to remember)
What causes stomatitis, vomiting, colic, and other GI signs, in addition to causing acute nephrosis in cows?
Inorganic mercurials
What do bones look like when affected by fluorosis?
Poritic, chalky, they spontaneously fracturw
Lets talk dogs...which are easy because they ant foreign objects to me (like cows are).
Dogs!
Which toxicity in dogs is associates with renal failure? What effects does this have on the animal?
Zn

Port wine urine
PU/PD
Which two toxicities result in wasting/cachexia in dogs?
Lead and copper
Congential liver defects in _____ can cause copper toxicity.
Bedlingtons
Skyes
Dobies
T/F. Cu toxicity causes a hemolytic crisis in dogs.
No! Acute acu toxicity --> hemolytic crisis in SHEEP, not dogs
With chroic lead toxicity vs acute lead toxicity, do GIT or CNS signs come first?
Chronic? GI then CNS
Acute? other way around
What could cause a pale brown nodular liver with yellow brown pigment?
Cu toxicity
What can cause exophthalmia in dogs?
Blindness?
Exophthalmia from Zn
Blindness from inorganic mercury
CS of inorganic mercury in dogs?
CNS excitation --> convulsions, uncontrollable chewing, blindness
Explain the CS of Zn.
Hemolytic anemia --> jaundice & hemoglobinuria --> renal failure --> pu/pd.
When might you see basophilic stippling and anemia in a dog?
Nucleated RBCs without anemia?
Both can be the result of lead toxicity
Whats a dog with chronic Cu toxicosis look like?
Thin, jaundiced, ascites
What might a dog with acute acu toxicity look like?
Vomiting and anorexia
What does bilirubin do at very low levels?
Scavenges singlet oxygen and peroxyl radicals