Cadmium Toxicity


Article Author:
Andrew Koons


Article Editor:
Venkat Rajasurya


Editors In Chief:
Silvio de Melo Jr.
Vittorio Giuliano
Truptesh Kothari


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
5/10/2019 4:07:31 PM

Introduction

Cadmium is a heavy metal that causes direct harm to humans in several forms.  It is regularly found with other heavy metals such as zinc, copper, and lead.  Concentrations increase due to soil disruption/volcanic activity and a byproduct of industrial processes.[1]  Industrially, its use is best known for electroplating and in the production of nickel-cadmium batteries.  

Etiology

Cadmium toxicity usually occurs after occupational, environmental, or hobby work exposure.  Environmental exposures can occur from contamination in the surrounding soil with the metal, and then the resultant food grown there is consumed.  This type of contamination can occur in areas where mining or refining of ores takes place. 

Something to this effect took place in Japan in the 1950s at the Jinzu River when a mine discharged a large amount of cadmium into the environment.  The rice grown in the area caused an epidemic of painful osteomalacia that occurred mostly in multiparous postmenopausal women.   The name given this condition was “itai-itai” disease which is “ouch-ouch” in Japanese since those affected would say this every time they took a step.[2]

Epidemiology

Welders, solderers, and jewelry worker are at risk for inhaling cadmium oxide fumes.  Significant toxicity is usually the result of metalworking in a closed space with improper ventilation.

Pathophysiology

Orally ingested cadmium is poorly bioavailable, but inhaled cadmium fumes are readily bioavailable.   Once in the bloodstream, cadmium binds to alpha-2-macroglobulin and albumin and gets distributed to the liver and kidneys.  Aside from these two main organs, cadmium also concentrates in the pancreas, spleen, heart, lung, and testes.[3]

Once in the liver, cadmium binds with metallothionein and this complex is slowly released from the liver.  Because of the slow release, its biologic half-life can be at least ten years. Cadmium then travels to the glomerulus, and large amounts concentrate in the proximal tubule–conferring its renal toxic effects.[4]

Histopathology

Metallothionein is protective, and the free cadmium cation is the damaging entity in this toxicity.  The cadmium ion causes mitochondrial damage via enzyme degradation and protein destruction.  This destructive effect makes the cell more susceptible to oxidative stress.  Also, cadmium affects cell adhesion and calcium transport that can lead to cell dysfunction and cell death.[5]

History and Physical

Acute Poisoning

Acute poisoning can occur by inhalation of cadmium fumes or ingestion of cadmium salts.  Cadmium pneumonitis can occur and look strikingly similar to metal fume fever.  Within six hours of soldering with cadmium alloys, patients may experience fever, chills, cough, and respiratory distress.  Patients may appear well on initial presentation but can progress from pneumonitis to acute respiratory distress syndrome (ARDS).  Death can occur in 3-5 days.  Survivors may suffer from lifelong restrictive lung disease.[6][7]

Acute ingestions occur more rarely than inhalational injury.  After ingestion, patients may develop gastrointestinal injury.  In high concentrations, it produces hemorrhagic necrosis of the gastrointestinal tract and multiorgan system failure.[8]

Chronic Poisoning

Nephrotoxicity

Most commonly, permanent proteinuria is seen after chronic cadmium exposure.  More specifically, beta-2-microglobulinuria is found in these workers.  Renal function has been reported to continue to deteriorate in some patients even after removal from cadmium contact[9].  Those with pre-existing renal disease or risk factors for developing renal disease (i.e., diabetes mellitus) are susceptible.[10]  Cadmium is also associated with hypercalciuria and nephrolithiasis.[11]

Pulmonary toxicity

The research is not clear on whether chronic cadmium inhalation causes pulmonary toxicity.  It is, however, agreed upon that exposure causes lung cancer.[12]

Musculoskeletal toxicity

Usually occurring after environmental exposure, painful osteomalacia has been seen mostly in postmenopausal women.  There appears to be a gender and age difference to those that are at risk.  This may account for the lack of occupational exposures as these workers tend to be younger men. 

Other organ systems

Hepatotoxicity is not reported with cadmium exposure likely because cadmium forms a complex with metallothionein which renders it inactivate.[13]  Neurologic dysfunction can occur in the form of parkinsonism, impaired higher cortical functioning, and olfactory disturbances.  Animal studies have shown a relationship with cadmium and hypertension, immunosuppression, and testicular dysfunction; however, these results have not translated to human studies.[14][15]

Evaluation

Cadmium blood concentrations have limited use other than for confirmation in acute exposure: history, physical exam, and symptoms guide diagnosis.  In chronic exposure, urinary cadmium is the test of choice to determine total body cadmium burden.  Anyone at high risk for chronic cadmium exposure should have routine urinary protein testing (beta-2-microglobulin).      

Treatment / Management

Acute Poisoning

Cadmium fumes pose a significant risk to the lungs.  Airway management is essential and supplemental oxygen applied.  Often, steroids area treatment of choice, though their benefit remains unproven. 

Ingestion of cadmium poses slightly different concerns.  Activated charcoal and gastric lavage are options.  The patient will require monitoring for gastrointestinal injury as well as renal and hepatic dysfunction.  Chelators, though promising, have not been definitively proven to be useful in cadmium toxicity.  However, it appears that if succimer is given early in the course, it has promising results.[16]

Chronic Poisoning

These patients will have a known exposure, and their dysfunction typically discovered on routine screening.  The first intervention is always to remove the patient from the exposure.  Chelation is not currently recommended for these patients even though the effects can be permanent and progressive. 

Differential Diagnosis

For any environmental or occupational metal exposure, one must consider the other prevalent metal toxicities such as iron, lead, arsenic, mercury, thallium.  In acute toxicities, other causes of pneumonitis and ARDS are on the differential; metal fume fever is a diagnosis of exclusion.

Prognosis

In acute exposure, restrictive lung disease can be lifelong.

In chronic exposure, kidney injury can be progressive and irreversible.  

Deterrence and Patient Education

If a patient's workplace or hobby puts them at risk for cadmium exposure, they should inform their doctor and make sure they are not experiencing lung, bone, neurologic symptoms.  Regular preventative measures would include urine screening for proteinuria, lung screening for cancer, and other tests to assure proper bone, cardiovascular, neurologic, and reproductive health.

Pearls and Other Issues

Current cadmium exposures come from electroplating, batteries, possible environmental exposures.

Acute exposure route is important:  Oral ingestion confers gastrointestinal injury and inhalation confers a severe chemical pneumonitis.

Chronic exposure is most characterized by nephrotoxicity in the form of proteinuria (beta-2-microglobulin), though there has also been a link to lung cancer.

Treatment is removal from exposure, supportive care, and succimer is a therapeutic consideration in acute cadmium salt ingestion; otherwise, chelation not recommended.

Enhancing Healthcare Team Outcomes

Managing cadmium toxicity requires a multidisciplinary approach in both acute and chronic exposures.  Prompt recognition of exposure is paramount and can affect the long-term prognosis of those exposed.  Nursing, emergency department physicians, occupational physicians, family medicine physicians, respiratory therapists, pharmacists, and laboratory staff all need to work collaboratively to ensure the best patient outcomes. 

  • Acute management of pneumonitis by the nurses, emergency physicians, and respiratory therapists
  • Recognition of chronic complications by the family or occupational physician for pulmonary function tests, urine microglobulin, etc
  • Pharmacy discussion and response for treatment with succimer

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Cadmium Toxicity - Questions

Take a quiz of the questions on this article.

Take Quiz
Exposure to which heavy metal is known to increase risk of prostate cancer?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Cadmium poisoning has been linked to which of the following processes?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Cadmium has been linked to several different forms of cancer. Which organ is the only one that is agreed upon by the International Agency for Research on Cancer (IARC) as at risk for carcinogenesis from cadmium exposure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A welder for 30 years at a battery factory presents to his primary care provider for routine follow-up. Which of the following tests is indicated to screen for their highest risk complication of chronic cadmium exposure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient presents 20 minutes after ingesting 10 grams of cadmium in a suicide attempt. Their kidney function is normal. Which of the following should be done next?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which test is most useful after known chronic cadmium exposure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Cadmium Toxicity - References

References

Godt J,Scheidig F,Grosse-Siestrup C,Esche V,Brandenburg P,Reich A,Groneberg DA, The toxicity of cadmium and resulting hazards for human health. Journal of occupational medicine and toxicology (London, England). 2006 Sep 10     [PubMed]
Kazantzis G, Cadmium, osteoporosis and calcium metabolism. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2004 Oct     [PubMed]
Cantilena LR Jr,Klaassen CD, Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion, and distribution of cadmium. Toxicology and applied pharmacology. 1981 May     [PubMed]
Barnhart S,Rosenstock L, Cadmium chemical pneumonitis. Chest. 1984 Nov     [PubMed]
Kazantzis G,Blanks RG,Sullivan KR, Is cadmium a human carcinogen? IARC scientific publications. 1992     [PubMed]
Houston MC, The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Alternative therapies in health and medicine. 2007 Mar-Apr     [PubMed]
Nordberg G,Jin T,Wu X,Lu J,Chen L,Liang Y,Lei L,Hong F,Bergdahl IA,Nordberg M, Kidney dysfunction and cadmium exposure--factors influencing dose-response relationships. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2012 Jun     [PubMed]
Pan YX,Luo Z,Zhuo MQ,Wei CC,Chen GH,Song YF, Oxidative stress and mitochondrial dysfunction mediated Cd-induced hepatic lipid accumulation in zebrafish Danio rerio. Aquatic toxicology (Amsterdam, Netherlands). 2018 Jun     [PubMed]
Anthony JS,Zamel N,Aberman A, Abnormalities in pulmonary function after brief exposure to toxic metal fumes. Canadian Medical Association journal. 1978 Sep 23     [PubMed]
Raval G,Straughen JE,McMillin GA,Bornhorst JA, Unexplained hemolytic anemia with multiorgan failure. Clinical chemistry. 2011 Nov     [PubMed]
Scott R,Patterson PJ,Burns R,Ottoway JM,Hussain FE,Fell GS,Dumbuya S,Iqbal M, Hypercalciuria related to cadmium exposure. Urology. 1978 May     [PubMed]
Haswell-Elkins M,Satarug S,O'Rourke P,Moore M,Ng J,McGrath V,Walmby M, Striking association between urinary cadmium level and albuminuria among Torres Strait Islander people with diabetes. Environmental research. 2008 Mar     [PubMed]
Chia KS,Tan AL,Chia SE,Ong CN,Jeyaratnam J, Renal tubular function of cadmium exposed workers. Annals of the Academy of Medicine, Singapore. 1992 Nov     [PubMed]
Ikeda M,Watanabe T,Zhang ZW,Moon CS,Shimbo S, The integrity of the liver among people environmentally exposed to cadmium at various levels. International archives of occupational and environmental health. 1997     [PubMed]
Rani A,Kumar A,Lal A,Pant M, Cellular mechanisms of cadmium-induced toxicity: a review. International journal of environmental health research. 2014 Aug     [PubMed]
Dan G,Lall SB,Rao DN, Humoral and cell mediated immune response to cadmium in mice. Drug and chemical toxicology. 2000 May     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Gastroenterology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Gastroenterology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Gastroenterology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Gastroenterology. When it is time for the Gastroenterology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Gastroenterology.