The list of toxins the human body can be exposed to is extensive. Since the list of toxins and their pathologic effects is so numerous, only some of the major toxins and their effects will be discussed in this chapter. Of these, by far the two most commonly encountered toxins are tobacco smoke and alcohol. In addition to a few major toxins, this chapter will also discuss very basic physical trauma and nutritional deficiencies.
The metabolism of xenobiotics (i.e., mechanism for removal of foreign substances such as drugs from the body) occurs via two phases. Phase I reactions involve attachment of polar functional groups to the substance, and phase II reactions involve conjugation of the substance. One important point concerning therapeutic implications is the concept that genetic variations in levels of cytochrome P-450 isozymes produce both “rapid metabolizers” and “slow metabolizers” and can result in toxic levels of medication in a patient on an otherwise normal therapeutic dose.
Constituents: Polycyclic aromatic hydrocarbons, arsenic, nickel, carbon monoxide, hydrogen cyanide, nicotine.
Effects of nicotine: Increased heart rate, increased blood pressure.
- About 30% of all cancer deaths and 90% of all lung cancer deaths are related to smoking.
- Pregnant females who smoke 10 or more cigarettes a day can induce hypoxia in their fetuses, which leads to complications that include decreased fetal weight and prematurity and to premature rupture of membranes and placental abruption at the time of delivery.
- Naïve users: 0.3 to 0.4 mg/dL can result in coma or death.
- Tolerant users: Can develop levels up to 0.7 mg/dL.
Complications of ethanol use by organ system
- Liver: Fatty change; hepatitis due to direct toxic effect of ethanol on hepatocytes; and cirrhosis, which occurs in only 10–15% of chronic alcoholics.
- Central nervous system (CNS): Thiamine deficiency, which may present as Wernicke encephalopathy (Figure 5-1) or Korsakoff syndrome (amnesia and confabulation). Morphologic features of thiamine deficiency include periventricular hemorrhage and petechiae of the mammillary bodies and cerebellar atrophy. Complications of ethanol use include alcohol withdrawal and associated delirium tremens.
- Cardiovascular: Dilated cardiomyopathy, hypertension.
- Gastrointestinal: Gastritis, pancreatitis.
- Reproductive: Fetal alcohol syndrome is associated with mental retardation, microcephaly, maxillary hypoplasia, smooth philtrum, short palpebral fissure, and atrial septal defects.
Wernicke encephalopathy. Note the punctate hemorrhages in the mammillary bodies. Wernicke encephalopathy is a complication of chronic alcohol abuse due to an accompanying thiamine deficiency.
Mechanism: Chronic alcohol use causes depression of α-receptors and β-receptors and enhances γ-aminobutyric acid (GABA), which serve as a stimulus to increase baseline neuronal activity. Therefore, when alcohol is withdrawn, patients have a sudden excited state of CNS activity ...