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Hematuria is seen as?

What toxins cause hematuria?
Hematuria is red/pink urine that the cells settle out if left to stand

anticoagulant rodenticides, chlorate, mercury, monensin, phenylbutazone, bracken fern (pteridium aquilinum), buttercup (Ranunculus spp.), Oak (Quercus spp), St. Johns Wort (Hypericum perforatum)
Hemoglobinuria is seen as?

What toxins cause hemoglobinuria
Red/pink urine that stays in serum when left to stand

Chlorate, copper, acetaminophen, phenothiazines, Brassica spp.
What causes brown black urine
Acorns (R/O azoturia in horses)
What causes Red urine
beets
myoglobin
Napthalene
What causes Red/ Brown urine
Methemoglobin
What causes Reddish gold urine
Billirubin- aflotoxins
blue green algae
Ragwort (Senecio spp. )
What causes Yellow urine
Dinitro compounds (old fashioned)
Carrots
What causes Orange urine
Paprika
What causes Green urine
Propofol
Cellular Injury & Death causes
Hypoxia
Membrane Damage
Free Radicals
How are free radicals formed
radiation energy
enzyme metabolism xenobiotics
redox reactions
How are free radicals neutralized
Unstable, decay
Antioxidants - Vit. A,C,E glutathione
Transition metals bind flavanoids
superoxide desmutase (SOD)
catalase
What do free radicals cause?
Lipid peroxidation- peroxidation of lipids in membranes - turn reactive & cause further damage

Protein damage - free radicals oxidize A.A.
Major groups of flavonoids
FLavones
flavonones
Catechins
Anthocycanins
Food sources Flavones and few examples
Apple skins, fruit peels, berries, broccoli, celery, onions, cranberries, grapes, lettuce, olives, parsley

examples: quercetin, myricetin, luteolin
Flavonones food sources & a few examples
flavonones are found in citrus fruits & peel

A few examples are narigin & taxifolin
Catechins food sources & a few examples
Redwine tea, cocoa

Catechin is an example
Anthocycanins food source & a few examples
Anthocycanins are found in berries, cherries, grapes, raspberries, red wine, strawberries, tea, dark fruit peels

A few examples are cyaniding, delphinidin, peonidin, malvidin, petunidin
Quercetin is a major flavonoid found in ...
onions, apples, berries, & broccoli
Quercetin uses
antioxidant and free radical absorber
synergistic w/ Vit. C or E
Can chelate metal ions & thus dec. hydroxyl free radical formation
some inhibit Mast cell formation (degranulate - modulate Ca channels)
True or false
Quercetin is more efficient than ascorbic acid at absorbing O2 radicals as it has 3 available hydroxyl rings & thus resulting oxidized compound is more stable
True
3 sites of action of poisons and phosphorylation
1. inhibitors of the ETC
2. block phosphorylation
3. uncoupling of oxidative phosphorylation
Poisons that block ETC & where
Piercidin A, barbituates: block transfer from FeS to Q. block enzyme linked NAD- dehydrogenase

Dimercaprol & Antimycin A block site 2 (cytochrome b-cytochrome C)

Carbon monoxide, H2S & Cyanide block sytochrome oxidase (site 3 proton pump)
Poisons that block phosphorylation
Oligomycin: Blocks F0F1 ATPase phosphoryaltion step.

Atractyloside (cocklebur (xanthium strumarium): blocks transport ADP in & ATP out

Organotin compounds
Poisons that uncouple oxidative phosphorylation
Energy goes to heat instead of phosphate bonds

dinitroorthocresol (DNOC)
pentachlorophenol (PCP)

m-chlorocarbonyl cyanide phenylhydrazone (CCP)

arsenates

2,4 D also allows leakage of H+ --> red. gradient
Aminoglycosydes, cephalosporins, amphotericin B, and NSAIDS all are toxic to what organ
Kidney
Aminoglycoside nephrotoxicosis is seen how ?
renal tubular necrosis, myeloid bodies, 2ndry lysosomes, proteinuria, reduced GFR. Mitochondria may be damaged and might see ARF in 5-7 days
Cephalosporin nephrotoxicosis is seen how?
reduced transport mechanism & glucose production. Raised BUN. Mitochondrial damage (red. mitochondrial respiration).

Lipid peroxidation also occurs.

Cephalosporin toxicity higher in Vit E/Sel deficient diets, also cephalosporin causes inc. diene products of peroxidation
Amphotericin B nephrotoxicosis is seen how
high lipid membrane binding = permeability affects
NSAID nephrotoxicosis affects the kidneys how
causes renal papillary necrosis. mechanism is unknown
Cyanide or rotenone do what to the liver
decrease tissue respiration --> hepatic damage and necrosis
Atractyloside from cocklebut (xanthium spp.) or dinitophenol does what to the liver
decreased cell energy = damage = hepatic necosis
Flouride
Ricin from Castor Bean (Ricinus communis) does what to the liver
causes interference with the RNA process --> liver damage and necrosis
CCL4 reduces incorporation of AA into lipoproteins. True or False

what does this do in the liver if anything
True

leads to liver damage and necrosis
What toxins cause macromolecule binding that leads to liver damage and necrosis
furosemide
acetaminophen
?- methyl drops
serum lipid peroxides rise in hepatitis, fatty liver & cirrhosis. E.g. of toxicants that do this
Carbon tetrachloride
phosphorus
ethano

lipid peroxidation from oxidative stress of molecular oxygen
an uncoupler of oxidative phosphorylation
DNP
an inhibitor of oxidative phosphorylation
atractyloside
cell defenses against free radicals can be depleted if the diet is deficient in ...
vitamin E, ascorbate , and carotenoids
what binds to sulfahydryl groups in glutathione
heavy metals
what can catalyse lipid peroxidation
iron and copper
what can reduce free radicals and regenerate Vitamin E
vitamin C
what protects membrane lipids against oxidative stress proportional to its content in the membrane
Vitamin E
what is a cofactor in mitochondrial dehydrogenases containing to SH groups for oxidation (protect against free radical by regenerating GSH)
Lipolic Acid
low levels it scavenges peroxyl radicals and deals with a singlet O2
billirubin
scavenge hydroxl groups & protects against hepatotoxicity
CHO
help provide SH in times of GSH depletion
sulfur containing AA
Acetominophen (paracetamol) toxicity is more common in which spp.

CS are ??
Cats

facial/ paw edema, dark chocolate (methylglobinemia) urine, cyanosis, dyspnic, depressed, hypothermic, V, anorexic, shallow respiration, icterus
Tx acetominophen toxicity
emetics
activated charcoal
purgatives (not w/ ulceration)
O2
** N-acetyl cystein "mucomyst" is the antidote.
Ascorbic acid converts metheglobin back to hemoglobin
glutathione precurspre are methionine & cyesteine
Can you see "apparent" recovery w/ acetominophen toxicity
Yes
Acetylsalicylic Acid is commonly called ...?

causes what in cats?
Aspirin

hepatitis
Chloroform & halothane produce

phenobarbital increases toxicity to

Halothane impairs what at high conc.
dienes

halothane

Ca transport
What is Phalloidin and what does it cause ?
fungal toxin

causes paralysis &dilatation of the bile canaliculi
what is Sporidemin ?

what does it cause?
mycotoxin (pithomyces hartarum)

causes Big Head - a fascial eczema -- photosensitization