What is the Biological Fate of Lead in the Body?

Learning Objectives

Upon completion of this section, you will be able to

  • Describe how lead is absorbed,
  • Describe how lead is distributed in the body, and
  • Identify the half-life of lead in the blood.
Introduction

The absorption and biological fate of lead once it enters the human body depends on a variety of factors.

The blood carries only a small fraction of total lead body burden, and serves as the initial receptacle of absorbed lead, distributing it throughout the body, making it available to other tissues.

Absorbed lead that is not excreted is exchanged primarily among three compartments:

  1. Blood,
  2. Mineralizing tissues (bones and teeth), which typically contain the vast majority of the lead body burden, and
  3. Soft tissue (liver, kidneys, lungs, brain, spleen, muscles, and heart).

These compartments, and the dynamics of the exchange between them, are discussed below.

Lead Absorption

Lead absorption depends on a variety of factors, including particulate size, route of exposure, nutritional status, health, and age of the individual.

  • Lead absorption can be impacted by route of exposure and is inversely proportional to the exposure particle size. For example, exposure to lead dust (respiratory route) may result in higher absorption than exposure to the equivalent amount of lead from chips (digestive route) of higher lead content paint.
  • Adults typically absorb up to 20% of ingested inorganic lead after a meal and up to 60-80% on an empty stomach [ATSDR 2010].
  • Children absorb about 50% of ingested lead after a meal [ATSDR 2010] and up to 100% on an empty stomach.
  • Most inhaled lead in the lower respiratory tract is absorbed.
  • Most of the lead that enters the body is excreted in urine or through biliary clearance (ultimately, in the feces).

The chemical form of lead or lead compounds entering the body is also a factor for the absorption and biological fate of lead.

  • Inorganic lead, the most common form of lead, is not metabolized in the liver.
  • Nearly all organic lead that is ingested is absorbed.
  • Organic lead compounds (those found in leaded gasoline and additives sold in the United States in the past) are metabolized in the liver.
Lead in the Blood

Although the blood generally carries only a small fraction of total lead body burden, it does serve as the initial receptacle of absorbed lead and distributes lead throughout the body, making it available to other tissues (or for excretion).

  • The half-life of lead in adult human blood has been estimated as 28 days [Griffin et al. 1975, as cited in ATSDR 2010] to 36 days [Rabinowitz et al. 1976, as cited in ATSDR 2010].
  • Approximately 99% of the lead in blood is associated with red blood cells; the remaining 1% resides in blood plasma [Everson and Patterson 1980 as cited in ATSDR 1999; EPA 1986b; DeSilva 1981].
  • The higher the lead concentration in the blood, the higher the percentage partitioned to plasma. This relationship is curvilinear – as blood lead levels (BLLs) increase, the high-end plasma level increases more.
  • On average, it requires slightly more than 1 year for children enrolled in case management with BLLs ≥10 micrograms per deciliter (μg/dL) to decline to <10 μg/dL [Dignam et al. 2008].

The Blood Lead Level is the most widely used measure of lead exposure.

These tests, however, do not measure total body burden of lead-they tend to be more reflective of recent or ongoing exposures (see “Clinical Assessment-Diagnostic Tests and Imaging: section).

Lead in Mineralizing Tissues (Bones and Teeth)

The bones and teeth of adults contain about 94% of their total lead body burden; in children, that figure is approximately 73% [Barry 1975, as cited in ATSDR 2010].

  • Lead in mineralizing tissues is not uniformly distributed. It tends to accumulate in bone regions undergoing the most active calcification at the time of exposure.
  • Known calcification rates of bones in childhood and adulthood suggest that lead accumulation will occur predominately in trabecular bone during childhood, and in both cortical and trabecular bone in adulthood [Auf der Heide and Wittmets 1992 as cited in ATSDR 2010].

Two physiological compartments appear to exist for lead in cortical and trabecular bone [ATSDR 2010]:

  • Inert component stores lead for decades, and
  • Labile component readily exchanges bone lead with the blood.

Under certain circumstances, however, this apparently inert lead will leave the bones and reenter the blood and soft tissue organs.

  • Bone-to-blood lead mobilization increases during periods of
    • Advanced age,
    • Broken bones,
    • Chromic disease,
    • Hyperthyroidism,
    • Immobilization (bedridden, etc.),
    • Kidney disease,
    • Lactation [Landrigan et al. 2002b],
    • Menopause,
    • Physiologic stress, and
    • Pregnancy.
    • Calcium deficiency exacerbates, or worsens, bone-to-blood lead mobilization in all of the above instances.
  • Consequently, the normally inert pool poses a special risk because it is a potential endogenous source of lead that can maintain BLLs long after exposure has ended.
Implications of Biological Fate

Symptoms or health effects can also appear in the absence of significant current exposure because lead from past exposures can accumulate in the bones (endogenous source).

  • In most cases, toxic BLLs reflect a mixture of current exposure to lead and endogenous contribution from previous exposure.
  • An acute high exposure to lead can lead to high short-term BLLs and cause symptoms of acute lead poisoning.

It is important that primary care physicians:

  • Evaluate a patient with potential lead poisoning,
  • Examine potential current and past lead exposures,
  • Look for other factors that affect the biokinetics of lead (such as pregnancy or poor nutrition), and
  • Rule out lead poisoning in cases of unexplained seizures or coma.
Key Points
  • Children absorb a higher percentage of ingested lead than adults.
  • Once in the bloodstream, lead is primarily distributed among three compartments – blood, mineralizing tissue, and soft tissues. The bones and teeth of adults contain more than 95% of total lead in the body.
  • In times of stress (particularly pregnancy and lactation), the body can mobilize lead stores, thereby increasing the level of lead in the blood.
  • The half-life of lead in adult human blood has been estimated as 28 days.
  • The body accumulates lead over a lifetime and normally releases it very slowly.
  • Both past and current elevated exposures to lead increase patient risks for adverse health effects from lead.