Cadmium

Distribution & Metabolism in the Body

Distribution

Cadmium is widely distributed in the body, with the major portion of the body burden located in the liver and kidney. Liver and kidney cadmium concentrations are comparable after short-term exposure, but the kidney concentration exceeds the liver concentration following prolonged exposure.

The concentration of cadmium in the liver of occupationally exposed workers generally increases in proportion to intensity and duration of exposures to values up to 100 µg/g. The concentration of cadmium in the kidney rises more slowly than in the liver after exposure and begins to decline after the onset of renal damage at a critical concentration of 160-285 µg/g.

Most non-occupationally exposed people are exposed to cadmium primarily through the diet. Cadmium can be detected in virtually all tissues in adults from industrialized countries, with greatest concentrations in the liver and kidney. Average cadmium concentrations in the kidney are at birth near zero , and rise roughly linearly with age to a peak (typically around 40-50 µg/g wet weight) between ages 50 and 60, after which kidney concentrations plateau or decline. Liver cadmium concentrations also begin near zero at birth , increase to typical values of 1-2 µg /g wet weight by age 20-25, then increase only slightly thereafter.

Metabolism

The most dangerous characteristic of cadmium is that it accumulates throughout lifetime. Cadmium accumulates in the liver and kidneys and has a long biological half-life, from 17-30 years in man. After uptake from the lung or the gastrointestinal tract, cadmium is transported in blood plasma initially bound to albumin, as shown in experimental animals. Cadmium bound to albumin is preferentially taken up by the liver. In the liver, cadmium induces the synthesis of metallothionein and a few days after exposure metallothionein-bound cadmium appears in the blood plasma. Because of its low molecular weight, cadmium-metallothionein is efficiently filtered through the glomeruli and thereafter taken up by the tubules. Cadmium accumulates in the human kidney over the entire lifetime. (reference)

Elimination

Most cadmium that is ingested or inhaled and transported to the gut via mucociliary clearance is excreted in the feces. Almost all fecal cadmium represents material that was not absorbed from the gastrointestinal tract. Most absorbed cadmium is excreted very slowly, with urinary and fecal excretion being approximately equal. Cadmium is also eliminated through hair and breast milk, but these routes are of limited importance for total excretion and do not significantly alter the biological half-time. (reference)

The placenta is only a partial barrier to fetal exposure to cadmium. Several studies have shown that in the general population urinary cadmium excretion increases with age, this increase coinciding with the increased body burden. Smokers have higher urinary excretion than non-smokers. The amount of cadmium excreted represents only a small fraction of the total body burden unless renal damage is present. Following oral exposure, the major proportion of administered cadmium is found in the feces, because absorption is low.

Half-life

Experimental and epidemiological evidence indicates strongly that the biological half-time in the whole body is extremely long (many years) For the human kidney half-lives ranged between 6 and 38 years, and for the human liver between 4 and 19 years. (reference)

Glomeruli are important acive groups in the pathway from the nose to the olfactory cortex. Each glomerulus receives input from olfactory receptor neurons expressing only one type of olfactory receptor. There are tens of millions of olfactory receptor cells, but only about two thousand glomeruli. In a remarkable example of convergence, glomeruli receive input from between five thousand and ten thousand olfactory receptor cells but only output onto ten to twenty five mitral cells. (reference)

Metallothioneins are proteins whose purpose is to metabolize and regulate metals. There are at least ten known closely related metallothionein proteins expressed in humans. In the human body, large quantities are synthesized primarily in the liver and kidneys. (reference)

Mucociliary clearance of the respiratory tract is an important defence mechanism against inhaled pathogens. Cilia, which line both the upper and lower airways, are covered by a thin layer of mucus, and beat rapidly in a coordinated fashion propelling particles trapped in the mucus layer to the pharynx. Defective mucociliary clearance predisposes the respiratory tract to recurrent infection, manifested by bronchiectasis and chronic sinusitis. (reference)