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Lead Toxicity
What is the Biological Fate of Lead?

Course: WB 1105
CE Original Date: August 20, 2007
CE Renewal Date: August 20, 2010
CE Expiration Date: August 20, 2012
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Learning Objectives

Upon completion of this section, you will be able to

  • describe how lead is taken up, distributed, and stored throughout the body
  • identify the half-life of lead in the blood.

Introduction

The absorption and biologic fate of lead once it enters the human body depend on a variety of factors including nutritional status, health, and age.

  • Adults typically absorb up to 20% of ingested lead.
  • 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 biologic 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 (far rarer today after EPA's ban on gasoline additives containing lead) are metabolized in the liver.

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

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

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

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 to be from 28 days (Griffin et al. 1975 as cited in ATSDR 2005) to 36 days. (Rabinowitz et al. 1976 as cited in ATSDR 2005)
  • Approximately 99% of the lead in blood is associated with red blood cells; the remaining 1% resides in blood plasma. (DeSilva 1981; EPA, 1986a; Everson and Patterson, 1980, as cited in ATSDR, 1999)
  • In addition, 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 as the high-end plasma level increases more.

Blood lead is also important because the BLL is the most widely used measure of lead exposure.

  • These tests, however, do not measure total body burden—they are more reflective of recent or ongoing exposures (see “Laboratory Evaluation 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, the figure is approximately 73% (Barry 1975 as cited in ATSDR 2005). 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 1999).
  • A new test to measure lead in bone (K-XRF, or K X-ray fluorescence) usually measures lead levels in trabecular bone at the patella or calcaneous and cortical bone at the tibia. However, this test is mostly used for research now.

Two physiological compartments appear to exist for lead in cortical and trabecular bone (ATSDR, 2005; ATSDR, 2000).

  • the inert component stores lead for decades
  • the 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 pregnancy, lactation, menopause, physiologic stress, chronic disease, hyperthyroidism, kidney disease, broken bones, and advanced age, all which are exacerbated by calcium deficiency.
  • 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

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

  • 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 lead poisoning.
  • It is important that primary care physicians evaluate a patient with potential lead poisoning, examine potential current and past lead exposures and look for other factors that affect the biokinetics of lead (such as pregnancy or poor nutrition).

Key Points

  • 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 body accumulates lead over a lifetime and normally releases it very slowly.
  • Both past and current elevated exposures to lead increase patient risks for lead effects.

   

Progress Check

6. What is the approximate half-life of lead in the blood?

A. seven days
B. thirty days
C. three to six months
D. one year

Answer:

To review relevant content, see Lead in the Blood in this section.

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