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Pathology of Cadmium Poisoning:

Cadmium is a known Human Carcinogen

Dr Sampurna Roy MD 

       

 

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Cadmium is an environmental pollutant and ranked as one of the most toxic substances.

It is found in tobacco, air and food.

Cadmium was first described by Friedrich Stromeyer (Göttingen, Germany) in 1817.

Cadmium intoxication can lead to kidney, bone, and pulmonary damages.

Cadmium is utilized in the manufacture of alkaline storage batteries, alloys, and electroplating of other metals.

Instances of inhalation of cadmium oxide fumes during welding steel parts that have been plated with a cadmium anticorrosive agent has been observed.

Because of its high rates of soil-to-plant transfer, cadmium is a contaminant found in most human foodstuffs.

Food is primary source of exposure among nonsmoking, nonoccupationally exposed populations. 

According to WHO a safe intake limit of 7 μg cadmium/week/kg body weight was set based on the critical renal cadmium concentration of between 100 and 200 μg/g wet weight that corresponds to a urinary threshold limit of 5 to 10 μg/g creatinine. 

Seafood may also be a source of exposure to heavy metals such as cadmium. Many types of seafood like crab are rich in cadmium, but the potential for toxicity after consumption is not clear.

Cadmium contained in cigarettes is an important risk factor for malignancy. 

Lungs:

Acute inhalation of relatively large concentrations of cadmium vapors produces acute cadmium pneumonia approximately 8 to 10 hours after inhalation of the vapors.

Histologically, lung is characterized by diffuse alveolar damage, with striking congestion and edema of the alveolar capillaries.

Death occurs in approximately 16% of those exposed to high concentration of the vapors.

Chronic inhalation of smaller amounts of cadmium vapors can result in interstitial fibrosis of the lungs.

This leads to the formation of honeycomb lung that is the result of repeated attacks of acute bronchiolitis and interstitial pneumonia with reparative scarring.

There are several reports of an increased incidence of emphysema in persons exposed to low concentration of cadmium fumes over a long period of times.

The cadmium contained in cigarettes is transmitted to the lungs during smoking.

One pack of 20 cigerattes contains 30 microgram of cadmium.

Cigarette smoking results in acute and chronic bronchitis and worsen the state of emphysema.

Emphysema may develop in cadmium smokers in the alkaline battery industry as a result of exposure to low concentrations of cadmium fumes over a long period of time.

Emphysema has been the major findings in the fatal cases of cadmium pneumonitis that have been studied.

Acute cadmium inhalation irritates the respiratory tract, with pulmonary edema the most dangerous result.

To properly assess the significance of the relationship of cadmium to the development of emphysema, further epidemiologic and other studies are required.       Doctor are you using social media ?

Kidney :

It is now certain that cadmium accumulates in the kidney with age and, if exposure is excessive and prolonged,  will induce a progressive form of chronic renal disease characterized by interstitial fibrosis and tubular atrophy.

Unlike the heavy-metal tubular dysfunctions brought about by damage to the proximal tubular cells, cadmium does not manifest tubular damage acutely but in a chronic sequence.

The tubular cell damage is in proportion to the increasing concentration of calcium bound to metallothionein.

Bonding of calcium and tissues and transport has been shown to be related to the presence of low-molecular-weight protein metallothionein.

There is a selective uptake by the proximal convoluted tubules of metallothionein-bound cadmium.

The toxic effects after a long-time exposure to the toxic levels of this union of cadmium with the protein metallothionein is characterized by damage to the plasma cell membrane resulting in the necrosis of tubular cells.

The effects of cadmium proximal renal function are characterized by increased cadmium in the urine, proteinuria (primarily Beta-2-microglobulin), aminoaciduria, glycosuria, and decreased renal tubular reabsorption of phosphate.

Urine sample

The most important measure of excessive cadmium exposure is increased cadmium excretion in the urine, and this finding reflects the concentration.

Studies of workers with cadmium exposure suggest that the “critical level” is a urine concentration of 10 to 15 mg, which means per gram of urinary creatinine.

At this level, proximal tubular reabsorption dysfunction will probably raise its ugly head.

Itai-itai disease: 

                             

Osteomalacia               Renal Tubular Disorder

It is the most severe form of chronic cadmium poisoning is caused by prolonged ingestion of cadmium.

It developed in many residents of the Jinzu River basin in Toyama Prefecture, Japan, an area severely polluted by cadmium that originated from a zinc mine located upstream. 

The disease primarily occurs in post-menopausal women and is mainly characterized by renal tubular disorder, which is known as tubulopathy and osteomalacia.

Cardiovascular System :

 

Cadmium in occupationally-exposed individuals appears to induce an increase in systolic and diastolic blood pressure and an increase in the prevalence of hypertension.

There evidence supports that cadmium, is a cardiovascular risk factor.

Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality.

Cadmium has also been associated with carotid atherosclerosis,  electro-cardiogram diagnosed myocardial infarction, self-reported ischemic heart disease, stroke, heart failure and peripheral arterial disease.

Cadmium related malignancy:

Cadmium and its compounds were classified as carcinogenic to humans.

Occupational cadmium exposure is associated with lung cancer in humans.

Cadmium exposure has also been linked to human prostate cancer.

Other target sites for cadmium carcinogenesis in humans include urinary bladder, kidney, liver, and stomach.

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer.

There is an increase in endometrial cancer risk among women with cadmium intake greater than an average value of 15 μg/day.

Cadmium is a nonessential metal that is known to accumulate in the human pancreas.

The major risk factors for pancreatic cancer (increasing age, cigarette smoking and occupations involving exposure to metalworking and pesticides) are all associated with increased exposure to cadmium.

 

Further reading:

Cadmium chemical pneumonitis.

Elevated urinary cadmium concentrations in a patient with acute cadmium pneumonitis.

Cadmium induced metal fume fever: results of inhalation challenge.

Cadmium, environmental exposure, and health outcomes.

The toxicity of cadmium and resulting hazards for human health

Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease.

Cadmium exposure and incident cardiovascular disease

Cadmium exposure and incident peripheral arterial disease.

Health effects of cadmium exposure--a review of the literature and a risk estimate.

Amount and metal composition of midgut gland metallothionein in shore crabs (Carcinus maenas) after exposure to cadmium in the food.

Seafood intake and blood cadmium in a cohort of adult avid seafood consumers.

Dietary exposure to cadmium and health effects: impact of environmental changes.

Cadmium exposure and incidence of diabetes mellitus - results from the malmö diet and cancer study.

Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review).

Cadmium and renal cancer

Cadmium and prostate cancer: a critical epidemiologic analysis.

Cadmium, lung and prostate cancer: a systematic review of recent epidemiological data.

Cadmium carcinogenesis.

Dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal women: a prospective cohort study.

Tissue levels of cadmium and trace elements in patients with myoma and uterine cancer.

Is cadmium a cause of human pancreatic cancer?

Cadmium exposure and liver disease among US adults.

WHO (World Health Organization) Evaluation of Certain Food Additives and Contaminants. Forty-first Report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series 837. 1993. 

IPCS (International Programme on Chemical Safety) Cadmium–Environmental Health Criteria 134. Geneva: World Health Organization; 1992.

 

 

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Dr  Sampurna Roy  MD

Consultant Histopathologist (Kolkata - India)

 

 


 

 

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