Introduction< ?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />
Lead serves no useful purpose in the human body, and its presence in the body can lead to toxic effects, regardless of exposure pathway. Lead toxicity can affect every organ system. On a molecular level, proposed mechanisms for toxicity involve fundamental biochemical processes. These include lead’s ability to inhibit or mimic the actions of calcium (which can affect calcium-dependent or related processes) and to interact with proteins (including those with sulfhydryl, amine, phosphate, and carboxyl groups) (ATSDR 1999).
- Acute high lead exposure can cause serious physiologic effects, including death or long-term damage to brain function and organ systems.
- Effects of lead exposure vary according to exposure timing and levels, and other factors, and some effects may be latent.
The blood levels at which health effects have been observed are discussed below. It must be emphasized, however, that these levels are constantly being revised as new data are generated, and that, for children, there may be no threshold for developmental effects. Overt clinical symptoms and health effects that come with high exposure levels can be distinguished on an individual basis by the practicing health care provider. However, lack of overt symptoms doesn’t mean “no lead poisoning.” Lower levels of exposure have been shown, through population studies, to have many subtle health effects. It is important to interdict all lead exposures.
The sections below describe specific physiologic effects associated with major organ systems and functions.
- Lead primarily affects the peripheral and central nervous systems, renal function, blood cells, and the metabolism of vitamin D and calcium. Lead can also cause hypertension, reproductive toxicity, and developmental effects.
The nervous system is the most sensitive target of lead exposure. Fetuses and young children are especially vulnerable to the neurologic effects of lead because their brains and nervous systems are still developing and the blood-brain barrier is incomplete. There may be no lower threshold for some of the adverse neurologic effects of lead in children; some of these effects have been documented at exposure levels once thought to cause no harmful effects (<10 µg/dL) (CDC 1997a). Because otherwise asymptomatic individuals may experience neurologic effects from lead exposure, clinicians should have a high index of suspicion for lead exposure, especially in the case of children.
- Effects in children generally occur at lower BLLs than in adults.
In children, acute exposure to very high levels of lead may produce encephalopathy and its attendant signs (e.g., hyperirritability, ataxia, convulsions, stupor, and coma or death). The BLLs associated with encephalopathy in children vary from study to study, but BLLs of 70-80 µg/dL or greater appear to indicate a serious risk (ATSDR 1999). Even without encephalopathy symptoms, these levels are associated with increased incidences of lasting neurologic and behavioral damage (ATSDR 1999).
- The developing nervous system of a child can be affected adversely at BLLs of less than 10 µg/dL. It is often impossible to determine these effects through clinical examination.
Children suffer other neurologic effects at much lower exposure levels. There is a large body of evidence that associates decrement in intelligence quotient (IQ) performance and other neuropsychologic defects with lead exposure. Some studies have found, for example, that for every 10 µg/dL increase in BLL, children’s IQ dropped by four to seven points (Yule et al. 1981; Schroeder et al. 1985; Fulton et al. 1987; Landsdown et al. 1986; Hawk et al. 1986; Winneke et al. 1990). There is also evidence that the probability of ADHD and hearing impairment in children increases with increasing BLLs, and that lead exposure may disrupt balance and impair peripheral nerve function (ATSDR 1999). These effects may begin at low, more widespread BLLs (at or below 10 µg/dL in some cases), and it may not be possible to detect them on clinical examination.
- There is a wide range of neurologic effects associated with lead exposure, some of which may likely be irreversible.
Some of the neurologic effects of lead in children may persist into adulthood. One study, for example, correlated lead exposure with lower class standing (classroom performance); greater absenteeism; more reading disabilities; and deficits in vocabulary, fine motor skills, reaction time, and hand-eye coordination in young adults more than 10 years after childhood exposure (Needleman et al. 1990).
There can be a difference in neurologic manifestations or sequelae between an adult exposed to lead as an adult, and an adult exposed as a child when the brain was developing. Childhood neurologic effects, including possibly ADHD, may persist into adulthood. Other than this, many of the neurologic symptoms experienced by children may also be experienced by lead-exposed adults, although the thresholds tend to be higher. Lead encephalopathy may occur at extremely high BLLs, e.g., 460 µg/dL (Kehoe 1961). Precursors of encephalopathy, such as dullness, irritability, poor attention span, muscular tremor, loss of memory, and hallucination, may occur at lower BLLs.
Less severe neurologic and behavioral effects have been documented in lead-exposed workers with BLLs ranging from 40 to 120 µg/dL. These effects include malaise; forgetfulness; irritability; lethargy; impaired concentration; depression and mood changes; increased nervousness; headache; fatigue; impotence; decreased libido; dizziness; weakness; and paresthesia; as well as diminished reaction time, visual motor performance, hand dexterity, IQ scores, and cognitive performance (ATSDR 1999). There is also some evidence that lead exposure may affect adults’ postural balance and peripheral nerve function (ATSDR 1997a, 1997b; Arving et al. 1980; Haenninen et al. 1978; Hogstedt et al. 1983; Mantere et al. 1982; Valciukas et al. 1978). Slowed nerve conduction and forearm extensor weakness (wrist drop), as late signs of lead intoxication, are more classic signs in workers chronically exposed to high lead levels.
- Lead exposure can lead to renal effects such as Fanconi-like syndromes, chronic nephropathy, and gout.
Many studies show a strong association between lead exposure and renal effects. Acute, high dose lead-induced impairment of proximal tubular function manifests in aminoaciduria, glycosuria, and hyperphosphaturia (a Fanconi-like syndrome); these effects appear to be reversible (ATSDR 1999). However, continued or repetitive exposures can cause a toxic stress on the kidney that, if unrelieved, may develop into chronic and often irreversible lead nephropathy (i.e., interstitial nephritis).
- Most lead-associated renal effects or disease are a result of ongoing chronic or current high acute exposure. They can also be attributable to previous chronic lead exposure.
The lowest level at which lead has an adverse effect on the kidney remains unknown. Most documented renal effects for occupational workers have been observed in acute high-dose exposures and high-to-moderate chronic exposures (BLL > 60 µg/dL). Currently, there are no early and sensitive indicators (e.g., biomarkers) considered predictive or indicative of renal damage from lead, and serum creatinine and creatinine clearance are used as later indicators. However, certain urinary biomarkers of the proximal tubule (e.g., N-acetyl-ß-D-glucosaminidase) show elevations with current exposures, even at BLLs less than 60 µg/dL; and some population-based studies show accelerated (i.e., greater than that for normal aging) increases in serum creatinine or decrements in creatinine clearance at BLLs below 60 µg/dL (Staessen et al. 1992; Kim et al. 1996; Payton et al. 1994). Some renal disease or decrement in renal function may be caused by latent effects of lead exposure that occurred years earlier. In children, acute lead-induced renal effects appear reversible, with recovery usually occurring within 2 months of treatment (Chisolm et al. 1976). Treatment of acute lead nephropathy in children appears to prevent progression to chronic interstitial nephritis (Wedeen et al. 1986).
It should be noted that end-stage renal disease is a relatively rare occurrence in the < ?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" />
Lead exposure is also believed to contribute to the onset of “saturnine gout,” which may develop as a result of lead-induced hyperuricemia due to decreased renal excretion of uric acid. In one study, more than 50% of patients suffering from lead nephropathy also suffered from gout (Bennett 1985). Saturnine gout is characterized by less frequent attacks than primary gout. Lead-associated gout may occur in premenopausal women, an uncommon occurrence in nonlead-associated gout (Goyer 1985). A study by Batuman et al. (1981) suggests that renal disease is more frequent and more severe when associated with saturnine gout than with primary gout.
- Lead inhibits several enzymes critical to the synthesis of heme, causing a decrease in blood hemoglobin.
Lead inhibits the body’s ability to make hemoglobin by interfering with several enzymatic steps in the heme pathway. Specifically, lead decreases heme biosynthesis by inhibiting δ-aminolevulinic acid dehydratase and ferrochelatase activity. Ferrochelatase, which catalyzes the insertion of iron int
