Lecture 25 Flashcards
Toxicant exposure is via inhalation and/or pulmonary circulation
_________ cardiac output passes through lungs
______ diffusion barriers that facilitate ____
exchange facilitate _______ uptake
_______ surface area for gas exchange = large surface area for _______ uptake
Total cardiac output passes through lungs
Thin diffusion barriers that facilitate gas
exchange facilitate toxicant uptake
Large surface area for gas exchange = large
surface area for toxicant uptake
Name the pulmonary defenses
Pulmonary defenses: mucus barrier,
mucociliary escalator system, active
immune system (bronchial associated
lymphoid tissue), toxicant metabolism, high
repair capacity
Name the acute, toxic responses:
◦ Airway reactivity
◦ Edema
Name the chronic, toxic responses:
◦ Emphysema
◦ Fibrosis
◦ Asthma
◦ Neoplasia
List the signs of respiratory toxicosis
Coughing
Nasal discharge
Epistaxis
Dyspnea, apnea, hypopnea, hyperpnea
Increased heart rate
Grunting
Weakness, confusion, fatigue, coma, death
List the sources of Ammonia
◦ Toxic air pollutant most frequently found in
________ concentrations in animal facilities
◦ Most common where _____ and other ______ are allowed to accumulate and decompose on solid floor
_____ hygiene conditions
The species most at risk are ______ and ______.
◦ Toxic air pollutant most frequently found in
high concentrations in animal facilities
◦ Most common where feces and other wastes are allowed to accumulate and decompose on solid floor
Poor hygiene conditions
Pigs and poultry
Name the species at risk of ammonia toxicosis
most, esp. poultry and pigs
What is the MOT of ammonia toxicity?
NH3 dissolves in ______ layer in the ____
and ______ respiratory tract to form ______
which is caustic and causes:
◦ Irritation of ___________ epithelium
◦ __________ of cells through disruption of cell
membrane ______ → __________ response
At concentrations found in animal facilities
(<_____ ppm) it causes chronic _______ to the
respiratory tract → secondary _______ infections and _______ growth
NH3 dissolves in aqueous layer in the eye
and upper respiratory tract to form NH4OH
which is caustic and causes:
◦ Irritation of respiratory epithelium
◦ Necrosis of cells through disruption of cell
membrane lipids → inflammatory response
At concentrations found in animal facilities
(<100ppm) it causes chronic stress to the
respiratory tract → 2o bacterial infections
and reduced growth
What are the clinical signs of ammonium toxicity?
Excessive tearing, shallow breathing, clear or
purulent nasal discharge
Increased secondary respiratory infections e.g.,
Bordetella rhinitis in pigs
Chickens may develop keratoconjunctivitis, corneal
opacity and tracheatis
Reduced production
Death at very high (>2500 ppm) exposure
concentrations
How do you Dx ammonium toxicity?
History
Field observations
How do you prevent and control ammonium toxicityT?
Adequate ventilation
Good sanitary conditions
What is the most common cause of human poisoning in the US?
Carbon monoxide
List the sources of Carbon Monoxide
◦ Odorless and colorless gas
◦ Byproduct of incomplete combustion of
hydrocarbon fuels esp. in the internal
combustion engine
◦ Gas water heaters, space heaters, or
furnaces in poorly ventilated spaces e.g.
farrowing houses and lambing sheds
◦ Fires
What is the MOT of carbon monoxide toxicity?
- Competes with O2 for binding sites on
__________
◦ Affinity of ____ for CO is 250× that for O2
◦ O2 carrying capacity of ___ is severely reduced
◦ Capacity to give off CO2 in the lungs is ______ - Increases affinity of O2 for ____ and the
stability of O2-___ bond
◦ O2 dissociation curve shifts to the _____
◦ Release of O2 from ___ to tissues is ______
Net effect = ______ availability of O2
to cells
Competes with O2 for binding sites on
hemoglobin (Hb)
◦ Affinity of Hb for CO is 250× that for O2
◦ O2 carrying capacity of Hb is severely reduced
◦ Capacity to give off CO2 in the lungs is reduced
Increases affinity of O2 for Hb and the
stability of O2-Hb bond
◦ O2 dissociation curve shifts to the left
◦ Release of O2 from Hb to tissues is impaired
Net effect = Reduced availability of O2
to cells
The Hb-O2 Dissociation Curves explains?
Explains how blood carries and releases oxygen
Mechanisms of Toxicity Cont.
Impairment of O2 transport by myoglobin
in a similar fashion as for Hb
Binds to cytochrome c oxidase in
mitochondria → interferes with cellular
respiration and causes generation of
reactive oxygen species → oxidative stress
Cytochromc C oxidase: Complex IV of the mitochondrial electron transport chain
What are the clinical signs of CO toxicosis
Signs @ >25% COHb; death @ >/= 60% COHb
Reflect hypoxia of tissues. Tissues with high
O2 demand (brain, heart and skeletal muscle)
are most impacted
Initially: drowsiness, nausea, vomiting, lethargy,
weakness, deafness (cats & dogs),
incoordination and cardiac arrhythmias
Cherry-red color to blood, skin and mucous
membranes due to high [COHb]
Severely affected animals: dyspnea, terminal clonic spasms, coma and acute death
Abortion
◦ CO crosses the placental barrier → fetal hypoxia
Chronic exposure to low levels results in
exercise intolerance and disturbances in
postural and position reflexes
How do you Dx CO toxicosis?
History suggestive of ____ exposure, e.g.,
_________ or faulty fuel burning ______
Clinical signs of _____ death and ______
Measure ____ in suspect environment
Measure _____ in blood
History suggestive of CO exposure, e.g.,
unvented or faulty fuel burning heaters
Clinical signs of acute death and hypoxia
Measure CO in suspect environment
Measure COHb in blood
How do you treat CO toxicosis?
Main goal: restore adequate _____ supply
particularly to the _____ and _____
◦ Decontaminate: move patient to an area of ____ air
◦ Establish and maintain _______ airway
◦ Provide artificial _______ if necessary
◦ Give _________ oxygen
◦ Give blood _________ for _______ Hb
Main goal: restore adequate oxygen supply
particularly to the brain and heart
◦ Decontaminate: move patient to an area of fresh air
◦ Establish and maintain patent airway
◦ Provide artificial respiration if necessary
◦ Give hyperbaric oxygen
◦ Give blood transfusion for functional Hb
Smoke is a complex mixture of vapors,
gases, fumes, heated air, particulates and
liquid aerosols
There is no typical smoke: composition of
smoke is highly variable
◦ Synthetic materials give rise to worse smoke in
terms of fume intensity and composition
Smoke inhalation is the leading cause of
deaths (>80%) from fires
◦ Primary cause of toxicity is carbon
monoxide inhalation
What is the ADME of paraquat toxicity?
Rapid but incomplete (dog: ___-___%)
absorption _____ with peak plasma conc. in ____ min.
Broken down _____ in GI tract
Preferentially concentrated in type __ & __
alveolar cells by a ________-_______
transport system
Excreted in _____ (largely __________)
Bioavailability is ________ by binding tightly to _____ → environmental persistence
Rapid but incomplete (dog: 25-28%)
absorption orally with peak plasma conc. in
75 min.
Broken down slowly in GI tract
Preferentially concentrated in type I & II
alveolar cells by a diamine-polyamine
transport system
Excreted in urine (largely unchanged)
Bioavailability is reduced by binding tightly to soil → environmental persistence
What is the MOT of Tryptophan toxicity
L-tryptophan is metabolized by ruminal
_________ to _____ → absorbed and concentrated in the ____
3-MI is metabolized by _________ ____ or
prostaglandin __ _______ (in ___ cells and
______, and type __ pneumocytes to a
lesser extent) to a toxic metabolite, _____
3-MEIN preferentially destroys ___ cells and
type __ pneumocytes → proliferation of type __ pneumocytes to restore the ______ epithelium
◦ During the proliferation period, type __ pneumocytes have ________ ability to synthesize and secrete functional surfactant. The surfactant produced does not effectively ______ surface tension
There is ________ alveolar permeability
resulting in edema
The alveolar damage is followed by ______
resulting in ______ interstitial pneumonia
a typical == No response to conventional therapy
L-tryptophan is metabolized by ruminal
microbes to 3-methylindole (3-MI) →
absorbed and concentrated in the lungs
3-MI is metabolized by cytochrome P450 or
prostaglandin H synthetase (in club cells and
macrophages, and type II pneumocytes to a
lesser extent) to a toxic metabolite, 3-
methyleneindolenine (3-MEIN)
3-MEIN preferentially destroys club cells and
type I pneumocytes → proliferation of type II
pneumocytes to restore the alveolar epithelium
◦ During the proliferation period, type II pneumocytes
have decreased ability to synthesize and secrete
functional surfactant. The surfactant produced does
not effectively lower surface tension
There is increased alveolar permeability
resulting in edema
The alveolar damage is followed by fibrosis
resulting in atypical interstitial pneumonia
a typical == No response to conventional therapy
Perilla frutescens (Mint Plant)
Ornamental, grows
around hog pens and in
shaded areas along
rivers/creeks
Widespread in
southern USA
