Page 254 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Respiratory Toxicity Chapter | 13 221

VetBooks.ir clear. However, parenchymal respiratory epithelial cells edema, as demonstrated by a case of fatal Taxus (Japanese
Heart failure is often associated with cardiogenic lung
could have transported particles toward the pulmonary
interstitium. Particles in the mammalian lung too small to
yew) poisoning in horses with pulmonary congestion,
be efficiently phagocytized were also transported into the hemorrhage and edema (Cope et al., 2004) as well as
lung’s interstitium. In bird lungs, there was a virtual calves given Nerium oleander (Oleander) clippings, which
absence of phagocytes; the absence may have caused the developed tachycardia and pulmonary edema (Galey
epithelial cells to take on a larger role. Following experi- et al., 1996).Very high levels of fumonisin (.100 ppm in
mental introduction of Sephadex or Freund’s adjuvant, diet) may cause fatal pulmonary edema in pigs 1 4h
phagocytes with physiological features similar to macro- after exposure (Marasas, 2001). Noncardiogenic pulmo-
phages can enter the bird’s pulmonary spaces. nary edema has been associated with airway obstruction,
Birds living in dusty environments—kiwis near the cranial trauma, seizures or electric shock (Drobatz et al.,
desert with abundant sand and polydispersed loose dust, 1995). In horses, hyper hydration prior to exercise may be
or birds living near or flying over volcanic ash—show detrimental to respiratory function due to some degree of
significant pathology and signs after only short exposures edema (Sosa et al., 2002). Laboratory rodents receiving
to small dust particles. Confined animal feeding opera- very high doses of paraquat may die with pulmonary
tions with poultry raised in high population densities often edema and hemorrhage (Witschi and Last, 2001).
show reduced production and pathology at necropsy Some toxic agents, such as alloxan, which denude the
(Brown et al., 1997). alveolar capillary unit, reduce the likelihood of recovery
(Witschi and Last, 2001), and may lead to significant col-
lagen deposition (Pickrell and Villegas, research commu-
LUNG INJURY nication). If the changes are intense and architecture is
severely compromised, pulmonary fibrosis may result.
Acute Responses to Lung Injury From some insults (histamine) an uneventful recovery
may result. Several other insults (e.g., paraquat) cause
Airway Reactivity
sufficient injury to lead to healing by secondary intent
Large mammalian conducting airways are surrounded by (fibrosis).
bronchial smooth musculature (BSM) (Witschi and Last, We determine the extent of pulmonary edema by relat-
2001). The muscle tone is modulated by the autonomic ing lung wet weight to body weight (Witschi and Last,
nervous system. Reflex contraction occurs after stimula- 2001). Alternatively, lungs, lobes, or slices can be
tion by irritants. Bronchoconstriction can also be pro- weighed before and after drying. The accuracy of the sec-
voked by cholinergic drugs. This stimulation is used in ond procedure is limited by the uniformity of the edema,
diagnosis as a basis to assess the “twitchiness” of BSM, but again this may be a useful indicator (Witschi and
i.e., at how low a level the bronchi can be induced to con- Last, 2001).
strict. These agents bind to receptors and trigger increased Acute respiratory distress, particularly acute pulmo-
intracellular cyclic monophosphates—adenosine and gua- nary edema, is treated with diuretics such as furosemide,
nosine, respectively (cAMP and cGMP). Histamine, pros- intranasal oxygen, bronchodilators, corticosteroids, and
taglandins, nitric oxide, and leukotrienes also influence alleviation of the underlying cause (Foreman, 1999). It is
bronchoconstriction. especially important to address the underlying cause in
many of these conditions. Furosemide was formerly used
in North America as a race-day preventive for exercise-
Pulmonary Edema induced pulmonary hemorrhage. The difficulty with using
Pulmonary edema is exudative, and it indicates acute lung furosemide as a preventive is that furosemide may also be
injury (Witschi and Last, 2001). Edema is associated with a performance-enhancing agent.
leakage or interruption, as well as thickening of the alveo-
lar capillary membrane. Edema fluid creates a thicker dif-
fusion barrier, and contributes to a mismatch of Nasal and Upper Airway Reactivity
ventilation to perfusion. The mismatch limits the rate of Upper airway irritant gases and particulates, especially
oxygen exchange from the air of the alveoli to the blood ultrafine particulates with greatly increased surface area,
of the alveolar capillaries, even if the alveolar capillary stimulate nasal (trigeminal) nerve endings (Witschi and
unit is normal in all other respects. Frequently, very Last, 2001). They also elicit avoidance reactions.
intense pulmonary edema will include some evidence of Phosphine (PH 3 ), e.g., is liberated after ingesting zinc
small pinpoint pulmonary hemorrhage. Even brief edema phosphide rodenticide; PH 3 irritates nasal and upper air-
may damage or denude epithelium, or endothelium, or way nerve endings resulting in avoidance reactions such
both. as breath holding and subsequent paroxysmal breathing