small inorganic quantities in body, methionine+cystein (protein bound) and taurine (free)

Glycosaminoglycans, Chondroitin sulfate (cartilage, bone, tendons, blood vessel walls)

Heparin sulfate (helps cell signalling)

non-ruminant animals (2week old piglets)

fed purified dietes containing 0.8% Met

tolerated 1/2 Met requirement being replaced by inorganinc sulfate

no effect on weight gain, feed efficiency or collagen content of tendons

some inorganic sulfate is present in forages

some rumen microbial species can incorporate sulfate into S-containing aa

 ...

sulfur requirements of rumen microbes (.16-.24%diet)

Sulfer not typically a problem in diets with an adequate level of protein

rumen bypass (protected) methionine

with insuffiecient S comes: reduced microflora, reduction in nutrient digestibility

reduced weight gain, appetite

decreased wool growth

dullness, weakness, emaciation

dairy cattle: decreased intake

DM digestibility, and milk production

decreased intake

poor growth

polioencephalomalcia

death

only found naturally in compounds (with something-like Potassium)

typically higher in forages than grains

animal products often contain more

common supplements: MgO, MgCl2, MgCO3, MgSO4

Mg toxicity not a practical issue

structural component of bone (60-70%)

bone ash .5-.7% Mg

bone contains stable and labile Mg store that accumulates with age

required for all phosphate transferrin systems

activator of all reactions requiring thiamin pyrophosphate (TPP)

enzyme activation (complexed with ATP, ADP, AMP) enzyme activatior in carbohydrate and lipid metabolism, binds messenger RNA to ribosomes

Arginase-metalloenzyme, Mg is a functional part (Urea cylce enzyme)

Vasodilation (reduce blood pressure)

Tetany (grass tetany or grass staggers) - hypomagnesemia

from spring flush (fresh spring forages)

includes involuntary contraction of muscles due to increased frequency of action potentials

nervousness/hyperiritability

tremors/convulsions

twitching of facial muscles

staggering gait

Magnesium enema, give 60g MgCl2 in 200 ml or water

Feed 1:1:1 MgO:TM salt:Grain

start 2 weeks before turning cattle out on pasture

limit time on pastures with spring flush

Hemoglobin/Myoglobin

oxidation-reduction (redox) reactions, electron transfer system

cytochromes and flavoproteins

80% functional in body (hemoglobin 65%, myoglobin 10%, Metalloenzymes 4%, Transferrin 1%)

20% stored (Ferritin 15%, Hemosiderin A 5%)

Green leafy materials (legumes or seed coats which are less available)

Phytase may increase acailability

feedstuffs of animal origin (high source)

Meat/bone/blood meal, meat

milk is a poor source

...

For most species, feed are adequate

supplements availability: ferric oxide 10%, ferroius carbonate 60%, ferrous sulfate 100%)

Baby pig anemia (most common)

low placental transfer of Fe, fast growth rate of piglets

clinical signs (pale skin, transparent ears, thumps)

Decreased #RBC assess hemoglobin and hematocrit

sows: unless kept outdoors, no access o soil or pasture (since milk poor source mus recieve supplement iron-iron dextran)

unthrifty appearance, listlessness, heavy breathing, enlarged heart, diarrhea (secondary symptom)

less to most available

(Cupric oxide, cupric chloride, cupric citrate, CuSO4 (tribasic copper chloride or TBCC), Cu-Lys (some instances = to CuSO4)

supplement rarely necessary

CuSO4-growth promotant (young pigs/chicks)

imporved weight gain, feed intake, and gain:feed

Fed at 50-250mg/kg diet

mechanism still unclear

Body contains 1.5-2.0ppm

highest in liver, muscle and bone

transported in blood as ceruloplasmin component (90% of Cu) Exretion route via bile

...

retentionin body decreased by (dietary phytate, high Ca, Fe, Zn, Mo, excretion into bile and feces)

Absorption:adult monogastrics: 5-10%, young animals: 15-30%, ruminant animals: 1-3%

controlled by rate of absorption

regulated by intestinal mucosa

Metallothiionein protein (Cu and Zn)-bound to Cys residues

absorption via active transporta and diffusion

Formation oxygen carring proteins (hemoglobin, myoglobin, hemocyanin)

Ceruloplasmin: feroxidase 1,6 Cu atoms)

conversion between Fe3+ and Fe2+ permits binding to iron transport protein (transferrin) and incorporationinto hemoglobin or myoglobin

...

formation of melanin (skin/hair)

activation amylase

maintain integrity of myelin sheath surrounding axons

cross-linking of connective tissues (collagen and elastin)

component of lysyl oxidation (OH group added to Lys to provide functional aspects of collagen and elastin)

cytochrome C oxidase-important in oxidative phosphorylation reaction (last step in elecrton transport chain)

Coponent of various oxidae enzymes (tyrosinase, amine oxidase, ascorbic acid oxidase, lysyl oxidase)

Poor growth, diarrhea, anemia

...

Nervous lesions: inability to coordinate bodyily movement

...

Depigmentation hair/wool

...

wool: decreased growth, tensile strenght, crimp (disulfide briges) and stringy or steely appearance

Menke's disease-deficiency due to impaired transport

mostly males-(<10 yrs life)

poor muscle tone, seizures, steel-colored hair that kinks

treat with daily Cu injections

...

Wilson's disease-Cu accumulation in tissues (liver and brain mostly)

hepatic faillure, neuropsychilatric illness, cardiomyopathy

treat: remove cu rom body or prevent Cu absorption

Penicillamine (Cys chelation of Cu)

Sheep very susceptible-maure ewes of British breed origin most vulnerable

accumulates in liver over a few weeks to a year

(1000-3000 ppm in liver but blood remains normal at .1-.2mg/dl)

sudden Cu release from hepatocytes precedes toxicity by 24-48 hours (blood Cu 500-2000 mg/dl leading to cell necrosis, jaundice, anemia, death)

CuMoO4 complex formed in GIT, reduces Cu absortion

copper levels as low as 10ppm can cause toxcity when molybdenu is low (<3pp)

dietary Mo tyically 1-3ppm, Cu:Mo of 10:1 or less will usually prevent toxicity

retaining trace mineral mix in diet is highly recommended (Zn, Mo will reduce Cu in liver)

toxicity often occurs when trae mineral supplements designed for cattle are fed to sheep

Holsteins tolerate 100ppm without a problem

Jerseys are susceptible to copper toxicity at >50 ppm

component of metalloenzymes

1) purine catabolism (Xanthine oxicase)

---> Uric acid

2) Aldehyde oxidase

reduction of cytochrome C (electron transport chain)

Not under practical conditions

no characteristic symptoms

requirement for rats and young chickens are less than .2ppm

Mo is a cofactor in enzyme xanthine oxidase (Mo raises uric acid leves)

Formation/excretion of uric acid explins some eculiarties of chickens

soil has .1-2.0ppm (avg=.3ppm)

high seleniferous soils (2-10ppm) potentially toxic to livestock (North/South Dekota)

...

Plants readily accumulate

astragalus genus (locoweeds and milk vetch)

Zylorhiza

woody aster

Oonopsis

Goldenweed

Lest to most available

Elemental Se, Selenite, selenate, se-yeast, Selenomethionine, Bo-Se (Injectable)

Metalloenzyme: glutathiione perozidase (ineraction of Se and vit E)

Synthesis of thyroid hormone (iodothyronine-5`-deiodinase: Se and I)

cell growth

Eicosanoid biosynthesis: synthesis of leukotrienes, prostaglandins and thrombozanes from arachidonic acid (20:4w6)

occurs at less than .1ppm

nutritional muscular dystropy (cardiomyopathy)-mulberry heart disease in pig, stiff lamb, white muscle disease calf)

Nonruminants: nerve degeneration adn edema-membrane degradation

symptoms

supressed immune system

impaired reproduction both sexes

chronic

hair loss, loss appetite, dullness, damaged hooves, stiffness of joints

Acute

Death from respiratiory failure, can arise from sudden exposure to high Se intake

allows <0.3ppm added selenium

Maximum tolerable concentration is 2.0ppm

regulaion stems from bioaccumulation data collected from California wetland habitats (Se toxcity noted in waterfowl)

1920's phosporus supplement used caused fluorine toxicity in animals (defluorinated rock phosphates)

1942-found correlation between F in drinking water and prevention community dental cavities

(addition F to drinking water and toothpast disrupts glycolytic pathway of bacteria)

Most plants have limited ability to absorb F from soil

forages contain 2-20ppm in a DM basis

Cereals and by-products: 1-3 ppm F

Major source for humans in water

Sources for animals is mineral supplements and feedstuffs of animal origin (bone/meat meal and meat)

bones and teeth

.02-.05% of apatite molecule

soft tissues and fluids rarely contain more than 2-4 ppm F

F causes apatite crystals to become larger, more resistant to acid

1 ppm-reduction in dental caries

2 ppm- mottled enamel

8 ppm- osteosclerosis (increased bone density), abnomal hardening

110 ppm- reduced growth, inhibitionof enolase in glycolysis

2 ppm is upper limit in water for livestock/poultry-can still cause mottling (dental fluorosis)

Serious toxicity at >5ppm

Chronic fluorosis in grazing livestock

continuous consumption high-F supplements

Drinking water high (3-5 or more ppm)

grazing on F-contaminated forages close to industrial plants

Known sources of supplement phosphate

Known sources of waer that could potentially cause toxicosis

Wells on ranches with known toxicity problems have water with 4-12 ppm F

constituent of vit B12

same deficiency symptoms same as B12

Deficiency symptoms due to deficiency in B12 not cobalt

Most feedstuffs contain adequate levels

soil deficiency primarily occurs in Florida and East coast states (Salt Sick) Co, Cu and Fe

wide safety margin between toxicity and requirement

toxicity unlikely under practical conditions due to low rate of Co absorption

Poorly retained in body (relative to copper)

heaviest element required by animals for proper physiological function

(thyroid gland 70-80%, muscle 10-20%, hide 4%, skeleton 3%, organs 5-10%)

Thyroid hormones:

Triiodothyronine T3 and Thyroxine T4 -> iodine accounts for ~60% of the molecular weight of these compounds

granular iodized salt and iodized salt block

deficiency

prevalent in humans and livestock

Goiter, enlarged thyroid gland

90% human goiter cause by deficiency

-> T3/T4 decrease-> TRH hypothalmus -> TSH pituitary -> growth of thyroid tissue

lead to an enlarged thyroidinterfere with synthesis T3/T4

Generally contained in crops beloning to Brassica family

Brassica rapa (field mustard), Canola (oilseed), ornamental cabbage

Canola-oil contain <5% erucic acid

Meal contain <3 mg/g glucosinolates

1. Enzyme activation (Mn2+)
2. phosphate transferases (carbohydrate metabolism)
3. decarboxylases
4. Enzymes involved in synthesis of mucopolysaccharides and glycoproteins

May be promoted by high dietary levels of Ca and P

reduced growth

depressed/delayed estrous and conception, increased abortion (cow/goat)

skeletal abnormalities, perosis (slipped tendon) in young chickens-> related to cartilage formation

located in skin, hair, wool (involved in keratinization)

accumulates in bone

componetn of metalloenzymes

1. carbonic anhydrase (most Zn in RBC)
2. pancreatic carboxypeptidase A/B (Most An in pancreatic juice)
3. lactate dehydrogenase

Insulin (stored as zinc complex)

activator of arginase and various peptidasesimportant for enzymes in volved in RNA/DNA synthesis, which ultimately affects brain development and IQ

controlled by rate of absorption

regulated by intestinal mucosa

with low-Zn most bound to Cys-rich intestinal protein (CRIP)

with high-Zn most bound t o metallothionein (contains Zn and Cu)

Dietary phytates

high levels Ca, Fe, Cu and Mo

excretion into pancreatic juice/feces

Decreased growth/appetiteAn deficiency aggravated by high Ca in dietskin lesions:reddening, eruption, scabs->parakeratosis

reduced feathering

reduced immune function

aluminum (Al)

Arsenic (As)

Cadmium (Cd)

Lead (Pb)

Mercury (Hg)

Lead/Arsenic most common in ruminants

plants/soils: mining/smelting region soil=2,500ppm arsenic...1,700ppm lead

Mineral ores can provide variable quanities of toxic elements

added to diet as:

clays (kaolin and bentonite) pellet binders

aluminosilicates: anti-cking agents

feedstuffs:

10-50ppm in grasses/clover

acid soils-can accumulate in plant

small amounts absorbed

excreted in feces

retained deposited in liver/ skeleton/brain/other tissues

kidneys major site excretion for absorbed Al

grazing cattle/ esp in tropics (soils low in P)

acidic soils (high concentration Al and Fe)

form insoluble phosphate-induces P deficiency

predominant cation in soils with pH <5

toxic to human brain: neurofibrillary tangles-Alzheimer's disease characteristic

5-9 times increase in cerebral cortex DNA in Alzheimer's patients

may be essential

most feed <.5ppm rarely >1ppm as-is

weed killers, cattle/sheep dips, insecticides, rodenticides and anthelmintics (dewormers)

wood treatment (green) for outside use-copper arsenic

soil contamination (mining/smelters)

arsenic in feeds rapidly absorbed and excreted in urin

can be stored in many tissues

vomiting, diarrhea, dermatitis (increased capillary permeability and cellular necrosis)

high levels in water cause poor growth, skin/hair problems

changes coat, weight loss, inflamed eyes, diarrhea, uncoordinated movement, inflamed mucous membranes of upper respiratory tract

may be essential

originates from Zn smelting and refining processes

plastics, pigments, batteries, metal alloys, commercial crop fertilizers containing phosphates, water ion galvanized or black polyethyene pipes

industrial sludge: fertilizer on agriultural land

feed phosphate deposits from florida typicallycontian 6-7 ppm cd

cadmium and lead

biosynthesis porphyrins, hemes, ctochromes

mobolize and release of Fe

Zn mines/smelters increase likelyhood of increased Cd intake

suggested <.5ppm, toxic 1-5ppm

adverse effects on metabolism of Ca, Cu, Zn and Fe

Symptoms similar to Zn deficiency

(decresed growth/eating, infertility, liver/kidney damage, scaly skin, anemia, enlarged joints)

affecting 46% adult birds in southern rocky mountains

calcium deficiency precipitated by Cd toxicity

willow plants found to be "biomagnifying" cadmium

environmental Pb can occur in plants, soil and water and may be a major hazard to grazing livestock

(rocks, vehicle exhaust, pipes, paints, soldered Cu pipe, batteries)

Pb smelting and mining areas can contaminate pastures and cropland with rainwater run-off

Gastrointestinal absorption, also via skin and respiratory tract

approx 40% of absorbed lead is deposited in skeleton and remains relatively immobile

also accumulates in liver and kidney

excreted in bile and urine

interferes with heme synthesis, leading to microcytic anemiaaccute toxicity is the main issue

inhibits enymes dependent on the presence of free sulfhydryl groups

impaired cardiac performance, neuronal degeneration, Polioencephalomalacia

pb mimics or replaces Ca at cellular and molecular level (inhibits neurotransmitter release)

use chelating agents to increases urinary excretion of lead and bile

loss of other essential minerals is a sideffect: Ca, Zn, Cu etc.) all +2 ions

Substances Generally Recognized as Safe

in order to qualify:

submit information to FDA

compilation available information on utility and saftey tha is normally in the published liturature

antibiotics

ionophores

anthelmintics (dewormers)

hormones

beta-agonists

coccidiostats

requires evidence that product is safe

Delaney Clause: not implicated to produce cancer (Selenium)

Kefauver-Harris Amendment: drug must have utility

National Environment Policy Act: no harmful effects on soil, plant, or animal life

Today...

proven safe and effective (target animal used as labeled)

Food must be safe for human consumption

FDA is responsible for enforcement: Delegated to Center for Veterinary Medicine

absence of...

residue in edible tissues

actue toxic effects

chronic physiological effect

mutagenic potential

carcinogenic potential

required...

efficacy

"against life"

bacteriostatic-prevent growth

bactericidal kill bacteria

modes of action:

control sub-clinical diseases, nutrient sparing effect, metabolic effects (more ATP)

feed-easy delivery mechanism

(swine/poultry)

reduce acid load placed on rumen when high levels of grain are fed or when hay and grain are fed separetely

(lactation dairy cows, feedlot cattle (during diet adjustment))

sodium bicarbonate most common

monensin reduces need for buffer (feedlot)

citric acid most common

lower stomach pH to improve protein digestion

helps reduce incidence of pathogens

Phytase (Most common)

releases phytate P

increases absorption and excretion P

Galactomannans common in poultry

increase feed efficiency

shifts energy partitioning from fat to lean tissue

(not antibiotic/hormone so no withdrawal period)

Paylean in pigs:finishing swine (last 28 days before market)

Optaflexx (ractopamine) for feedlot cattle (most effective) 28-42 days

Immunocastration: Improvac

vaccine against gonadotropin releasing hormone

2 injections first anytime, 2nd 4-6 weeks before harvest

improve growth rate, feed efficiency, protein deposition

peptide-TRH

Lipid and phospholipid-derived (steroid, testosterone, etc)

Monoamines-from aromatic aa (thyroxin, epinepherine)

24 FDA approved

Melengesterol acetate (MGA)-only hormone feed additive

synthetic progestin, prevents estrus behavior, improves gain and feed efficiency, no withdrawal period

often labeled as a class of antibiotics that allows ions to move through cell membranes of gram-positive bacteria

...

increases propionate and decreases acetate in rumen

...

monensin-80% market (methane production, prevents coccidiosis, improves growth and feed efficiency, increased meal frequency)

lasalocid and laidlomycin

not absorbed in ruminants

horses do absorb

very toxic and no treatment

chelated: metal and aa bound by covalent bond

cost 3-5times more than inorganic sources of same mineral, response is inconsistent

Proteinated: metal and aa or peptide bound together

low interaction with other minerals

increase repro, immune, hoof integrity, decreases somatic cell count

feed 1/3 organic and 2/3 inorganic trace mineral

antioxidants prevent oxidative rancidity

inhibitors of molds and bacteria

specific microbial cultures that increase that populations of "good bacteria" in the gut

suppress pathogenic species

stimulate immune function

responds best:

under stress, newly weaned, relocated, off feed for period

excellent source B-vit

source of mannan-oligosaccharides that bind lectins on cell wall of undesirable bacteria

enhanced immune response

high producing cow gives most consistent response

high levels readily fermentable carbohydrates consumed

(Grain or rumen overload)

lactic acid acidosis

saliva is a basic solution (buffer)

rumen has no mucous membrane-acid damage easy

typical 12-48 hours to develop..death in 48

...

increase roughage level (increases saliva production)

...

provide alkaline agent nutralize excess volatile fatty acid

baking soda (NaHCO3) .75% diet

empty rumen/replace content from healthy animal

...Prevent...

>10% roughage in finishing rations

use buffers and neutralizers

molds/fungi produce metabolites called mycotoxins

...

B1,B2,G1,G2

...

conditions for developent..temp 75-90

moisture >13%

insect damage crop

mechanical damage seed/grain

poor performance

diarrhea

liver leasions

enlarged kidneys

necrois of renal tubes

death

(0% tolerance in dairy)

can pass into milk of animals that consume contaminated feedstuffs...milk must have less than .5ppb

ammoniation

must be fed to ruminants

mix contaminated products with clays-will be secreted in feces bound to clay

can't belch

dry/free gas

obstruction of esophagus, over-filling, paralysis rumen

frothy/pasture bloat

ggas trapped in frothy rumen contents

soluble proteins and Saponins from legumes (clover, alfalfa), insufficient saliva production when young, saliva has antifoaming properties

shows: left side

depends on degree, relieve gas

break up foam (mineral oil or feed)

preventatives

feed high roughage rations

avoid finely ground grains

add anti-foaming agents

long grass roughage, free choice

no young alfalfa

mad cow

abnormal protein folding (prion)-very resistant to denaturation

3-10 year incubation

great britain 92-93 epidemic

FDA banned feeding ruminant meat and bon meal back to ruminants

abdominal pain

Gas: over consumptionn lush grasses, cecum becomes filled with gas due to high fermentation rate

Impaction-caused by excessive consumption of grain or lush, lack water intake

Sand-sandy soil, impaction in cecum

overeating disease

sheep most susceptible

cause: Clostridium perfingens, which is normally in GIT and soil

occurs following large intake carbohydrate (starch) or rapid change to a high-starch diet

100% mortality, 24hours

vaccination only prevention

staggering, convulsions, listlessness, coma

dairy cow-1-6 weeks after calving

overly fat cows

twin lamb disease

last month before lambing

off feed and severely hypoglycemic, decreased milk production, acetone smell, death

(prevent in cows, with high energy diet, and weight manangment...in sheep, diet least 30% concentrate last two months gestation)

rotation and/or sinking of the coffin bone

excesss grain consumption is the most common cause

toxins released after (excess water, retained placenta, too much grain) tend to accumulate in extremities and destroy the laminae

inflammation of the laminae of hoof

laminae connect hoof to coffin bone

to prevent

2.0 grams phenylbutazone/1000 lbs twice daily

give antihistamine and diuretics

proper shoeing

consumption No3-converstion to NO2 - production NH3

NO2 accumulates in rumen and blood

Methemoglobin FE3+ cannot tansport oygen which leads to death by asphyxiation (1-2% normal, above >10% bad)

young plants have higher concentration

lower plant portion has highest concentration

drought damaged corn silage

heavily fertilized wheat, rye, sundangrass, sorghums

weeds, (johnsongrass, nightshade, ragweed)

breed: Bedlinton terrier, Doberman pincher, West Highland white terrier

lethargy, anorexia, vomiting, abdominal pain

Treatment:restricted diet, chelating agents increase urinary ecretion of Cu, An acetate, blocks intestinal absorption of Cu

dry cow fed high Ca and low P

Parathyroid gland becomes sluggish

(requires hormone to mobilize bone Ca)

when calves, parathyroid slow to respond

Hypocalcaemia

occurs within 3 days of mature cow giving birth

paralysis in hind legs ($10milion/year dairy industry)

Ca requirment increased for lactation

excerises the parathyroid gland

feed anionic (high Cl, PO4, SO4) diet during dry period

feed Ca deficient diet for 10-15day before calves

20 million IU of vitD per cow no more than 7day before calving

causes

infection (rare)

tumor

urethral plugs

uroliths (crystals) most common (calculi)-struvie (mg, ammonium, phosphate)

calcium oxalate, calcuim phosphate, uric acid

Prevent

feeding schedule, water balance, acidify food, magnesium intake

steers and wethers fed high grain (esp sorghum grain)

treatment

inefective, feed ammonium chloride

1.5% salt feed

give muscle relaxants

surgery

Prevent

feed adequate calcium

maintain 2:1 Ca:P

feed 1-1.5 oz, ammonium chloride daily