Toxicology Lecture 8 Salt, Nh4, O-Po4 Toxicity

Front 1

What are 5 sources of sodium (salt)?

Back 1

1) Added to feed
2) In milk replacers
3) Sea water
4) Oil field run off
5) Salt water lakes

Front 2

What are 6 possible reasons for a lack of fresh water?

Back 2

1) Frozen watering devices
2) Broken pipes or watering devices
3) Draught
4) Neglect to supply water
5) *Only water supplied in feed
-pig slop, milk replacements for calves, tube feeding
6) unpalatable water or can't find water

Front 3

What is the order of susceptibility of poultry, cattle and swine to getting salt poisoning bc the only water available contains excess salt?

Back 3

Swine > poultry > cattle

Front 4

What is the normal need for water per kg of dry feed?

Back 4

2-3 L of water / kg of dry feed

Front 5

How much salt should be in the feed?

Back 5

0.5 to 1% salt in ration ok, normal
-10% salt in ration not toxic if unlimited amount of fresh water available

Front 6

Water containing > ____% of salt will be toxic if it's the only source of water.

Back 6

1%

Front 7

What is the toxic dose of salt that causes acute toxicity in cattle?

Back 7

2.2 g/kg

Front 8

What is the toxic dose of salt in sheep that results in acute toxicity?

Back 8

4 g/kg

Front 9

What is the mechanism of action of salt poisoning?

Back 9

High levels of Na in brain inhibit anaerobic glycolysis
-Brain doesn't function
-Can't remove Na from brain

Front 10

What happens when you give water to an animal w/ salt poisoning?

Back 10

Renal excretion of Na increases so blood Na is reduced, but brain Na levels remain high therefore the osmotic gradient draws water to brain causing cerebral edema

Front 11

What are the 6 clinical signs of salt poisoning in calves?

Back 11

1) Hyperesthesia (touch them and they jump)
2) Muscle twitching
3) Nystagmus
4) Kicking at phantoms
5) Opisthotonus
6) Convulsions
-not regular like in swine

Front 12

What are the 6 clinical signs of salt poisoning in swine?

Back 12

1) Head shaking, nodding
2) Backing up fast
3) Rear collapses, sitting and head nodding
4) Falls to side w/ convulsion
5) Rest, recovers, gets up, looks weak but normal
6) Repeated at intervals (+/-7 minutes)

Front 13

What are the 5 clinical signs of salt poisoning in foals?

Back 13

1) Muscle twitching
2) Weakness
3) Seizures
4) Dehydration
5) Other CNS signs
-Head pressing, blind, paddling

Front 14

What are 3 digestive signs of salt poisoning?

Back 14

1) Thirst
2) Constipation or diarrhea
3) Salivation

Front 15

What are 3 CNS signs of salt poisoning?

Back 15

1) Dullness
2) Ataxia, knuckling
3) Excitable, aggressive

Front 16

What are 3 DDX for salt poisoning in a calf?

Back 16

1) Hypomagnesemic tetany (milk tetany)
2) PEM
3) Other neuro-toxins, lead, chlorinated HCs

Front 17

What is a differential diagnosis for salt poisoning in swine?

Back 17

Other CNS toxins, or encephalitis

Front 18

What are 2 differentials in poultry?

Back 18

Depression, collapse

Front 19

How do you diagnose salt poisoning?

Back 19

-Serum Na 160-210 mEq/L
-Serum Cl also increased
-Anion gap & total protein increased
-CSF Na> serum Na (or above 160 mEq/L)

Front 20

What are the 3 histologic lesions seen of the brain in cases of salt poisoning?

Back 20

1) Edema & necrosis
2) Perivascular cuffing cerebral cortex
3) ***In swine eosinophilic perivascular cuffing (in cattle mononuclear cuffing)

Front 21

**What is a pathognomonic lesion of salt poisoning in swine?

Back 21

Eosinophilic perivascular cuffing

Front 22

**True or false. Water should be immediately supplied to animals with salt poisoning.

Back 22

False!!! Supplying water may make worse
-Remove sodium without casing cerebral edema

Front 23

What is the treatment for salt poisoning?

Back 23

NOT GIVING WATER
-IV saline or slightly hypertonic saline
-IV mannitol
-IV glycerine
-Diazepam for seizures

Front 24

How can you prevent animals from getting salt poisoning?

Back 24

FRESH WATER
-< 5000 ppm of salt

Front 25

What are 6 sources of non protein nitrogen?

Back 25

1) Feed grade urea
2) Feed grade biuret
-2 molecules of urea condensed
3) Diammonium phosphate
4) Ammonium polyphosphate
5) Ammonium sulfate
6) Monoammonium phosphate

Front 26

What is the mode of action of urea poisoning?

Back 26

-Urea and other NPN converted to *ammonia by bacteria in rumen
-Ammonia exceeds amount microbes can use for protein production
-Ammonia absorbed--> hyperammonemia
-Overwhelms liver's ability to convert to urea
-Inhibits citric acid cycle ---> metabolic acidosis

Front 27

How is urea metabolized?

Back 27

Converted to ammonia by rumen micro-organisms

Front 28

What happens to ammonia produced by urea metabolism?

Back 28

Used by bacteria to make microbial protein

Front 29

What happens if there's too much ammonia or microbes can't adjust to the amount of ammonia?

Back 29

Ammonia will accumulate and be absorbed, liver may become overwhelmed in its ability to convert ammonia to urea

Front 30

What is the urea cycle?

Back 30

-Urea produced by liver from NH3
-2NH3 + CO2 --> NH2-C=O-NH2 + H2O
-Urea excreted by kidney in monogastric
-Excreted into rumen and saliva in ruminant
-In rumen urea ---> NH3--> microbial protein

Front 31

What are 2 sources of ammonia within the body?

Back 31

1) Deamination of amino acid
2) Absorbed from rumen--> portal v.--> liver

Front 32

What are 6 circumstances (ways of causing) of urea poisoning?

Back 32

1) Too much urea or other NPN added to ration or *changed too quickly
2) More than one source of NPN or ammonia
3) Feed not mixed properly
4) Too much in lick tanks w/ molasses
5) Ammonia added to poor quality forage at > 3%
6) Not enough energy feeds for the microbes to use in making microbial protein

Front 33

The toxic dose of urea varies with what 2 factors?

Back 33

1) Adaptability of microbes to utilize in protein production
2) Amount of energy feed available to provide VFA to combine w/ ammonia to make amino acids

Front 34

What is the approximate toxic dose of urea? Ammonium salts?

Back 34

Urea: 0.3 - 0.5 g/ kg BW
Ammonium salts: 1-2 g/kg

Front 35

Urea is not very toxic in ____ animals.

Back 35

Monogastric

Front 36

What is the pathophysiology of urea toxicity?

Back 36

-Excess ammonia in rumen
-Absorbed due to concentration gradient (high pH--> unionized)
-Hyperammonemia
-Toxic to citric acid cycle
-Metabolic acidosis
-Lactic acidosis & hyperkalemic heart failure

Front 37

**What is the most distinct sign of urea poisoning in cattle?

Back 37

Weakness with *front end paresis
-Usually weakness starts in back

Front 38

How long does it take signs from urea poisoning to develop?

Back 38

1/4-6 h after ingestion

Front 39

What are the 6 clinical signs of cattle with urea poisoning?

Back 39

1) Salivation
2) Odontopresis (grinding teeth)
3) Colic
4) Muscle tremors
5) Weakness- front end paresis*
6) Down, bloat, regurgitation, hyperthermia, cyanosis, death

Front 40

**What about the lab data of cattle with urea poisoning allows for a diagnosis?

Back 40

Metabolic acidosis
Rumenal alkalosis
**Only condition where see different conditions in rumen and blood

Front 41

There will be an increase in what 5 pieces of lab data in an animal with urea poisoning?

Back 41

1) Blood glucose
2) Lactic acid
3) Potassium
4) BUN
-Liver still alright so converting as much ammonia as possible into urea
5) AST (m damage)

Front 42

What 3 DDX for the salivation caused by urea poisoning?

Back 42

Lesions in mouth
Choke
Other toxins

Front 43

What 3 diagnostic tests should be performed to diagnose urea poisoning?

Back 43

1) Blood ammonia 1-4 mg/ 100 mL
2) Rumen ammonia > 80 mg/100 mL
3) Rumen pH> 7.5
-limited DDX for this

Front 44

What are 2 things you can do to treat urea poisoning?

Back 44

1) Treat metabolic acidosis
-IV NaHCO3
2) Try to acidify the rumen, prevent NH3 absorption
-Vinegar
-Cold water in rumen

Front 45

What are 4 ways to prevent urea toxicity?

Back 45

1) Limit urea or NPN in ration
2) NPN supply <30-40% of protein
3) Don't use on young animals, ammonia utilizing organisms not developed
4) Ruminannts quickly lose adaption to NPN

Front 46

What are the main sources of organophosphate toxicity?

Back 46

-Insecticides and some anthelmintics
-Carbamates

Front 47

What are 4 ways that an animal can get organophosphate toxicity?

Back 47

1) Overdose
2) Combined w/ other anti-cholinesterases
-i.e. flea collar, fly tags, insecticide, antihelmentic, crop dusting
3) Accidental exposure
-in feed
-Crop dusting
4) Potentiated w/ other cpds

Front 48

What is the mode of action of organophosphate toxicity?

Back 48

Combines w/ and inactivates cholinesterases
-terminates continued stimulation on cholinergic receptors
-If limited cholinesterase activity: continued cholinergic stimulation

Front 49

What are 3 locations where there will be continued cholinergic stimulation from organophospahte toxicity?

Back 49

1) Preganglionic sympathetic & pre & postganglionic parasympathetic
2) Postganglionic parasympathetic to organs
3) Motor nerves to muscles

Front 50

What are the 3 types of cholinesterase present in the body?

Back 50

1) True cholinesterase at nerve endings
-Takes time to regenerate
2) True cholinesterase in Erythrocyte
-Doesn't regenerate until RBC replaced
3) Pseudo-cholinesterase in plasma & organs
-Produced by liver
-Takes 4-7 d to regenerate

Front 51

What is a big difference b/w organophosphate and carbamate toxicity?

Back 51

Organophosphates form a permanent bond after "aging" and carbamates form a reversible bond

Front 52

What are 3 ways that organophosphates are absorbed?

Back 52

Oral, dermal, inhalation

Front 53

How is the distribution of organophosphates different from that of organochlorines?

Back 53

Distributed rapidly but not stored in fat like organochlorine

Front 54

What are organophosphates metabolized into?

Back 54

More toxic oxygen analog
-Excreted rapidly but some persist longer if soluble in fat

Front 55

What are 5 things that can potentiate the effects of anti-cholinesterases?

Back 55

1) **Testosterone
-bulls r more susceptible
2) Ptz type tranquilizers
3) Succinylcholine
4) Nicotine and curare
5) Aminoglycoside antibiotics

Front 56

What is the lethal dose of organophosphates?

Back 56

Varies w/ agent
-Over 200 organophosphates
-Some toxic at 1 mg/kg
-Some need to be activated

Front 57

How long does it take for the onset of clinical signs of organophosphate toxicity to appear?

Back 57

Delayed, 18-30 h
-Varies w/ compound

Front 58

What are 7 clinical signs of organophosphate toxicity?

Back 58

1) Salivation
2) Lacrimation
3) Diarrhea
4) Miosis
5) Muscle twitching, fasciculations
6) Dyspnea
7) Bradycardia

Front 59

What can follow fasciculations from organophosphate toxicity?

Back 59

Paralysis

Front 60

What may happen to an animal w/ organophosphate toxicity after CNS stimulation?

Back 60

May be followed by depression

Front 61

What are 5 clinical signs of organophosphate toxicity from chlorpyrifos (Dursban) pour on?

Back 61

1) Depression
2) Rumen atony
3) Bloat
4) Diarrhea
5) No salivation or miosis

Front 62

How long does it take for the clinical signs of toxicity from Chlorpyrifos (dursban) to develop?

Back 62

Signs are delayed takes 4-7 days

Front 63

What are the 4 DDX for organophosphate toxicity?

Back 63

1) Other anticholinesterase agents
2) Cholinergic stimulation
3) Some poisonous plants
4) Other causes of rumen atony & bloat

Front 64

What causes the delayed neuropathy related to organophosphate toxicity?

Back 64

Not related to cholinergic stimulation
Occurs 7-21 days after exposure (after "aging")

Front 65

What are the 4 clinical signs of delayed neuropathy from organophosphate toxicity?

Back 65

1) Weakness
2) Ataxia
3) Conscious proprioceptive deficits
4) Paralysis

Front 66

What are the lab findings of an animal with organophosphate toxicity?

Back 66

Non-specific clinical pathologic parameters
-Increase PCV
-CK & AST elevated
-Hyperglycemia
-Hypokalemia
-Increased neutrophils

Front 67

What are 3 diagnostic tests that can be ran specifically to try and diagnose organophosphate toxicity?

Back 67

1) History of exposure
2) Plasma pseudo cholinesterase levels
-Usually <30-50% of normal
-Timing is important bc regenerates
3) RBC (whole blood) cholinesterase

Front 68

What are 4 things that can be done to treat organophosphate toxicity?

Back 68

1) Wash w soap
2) Activated charcoal
3) Atropine counteracts muscarinic signs
4) Oximes; 2-PAM

Front 69

How do oximes help treat organophosphate toxicity?

Back 69

Competes w/ and displaces organophosphate from Ach-esterase bonding cite
-Also inactivates acetylcholine esterase when attached
-Must give before aging

Front 70

Should you use oximes to treat carbamate toxicity? Why or why not?

Back 70

No reversal is spontaneous

Front 71

What are 2 ways you can prevent organophosphate toxicity?

Back 71

1) Don't use several anti-cholinesterase agents at the same time
2) Store and label and use insecticides safely