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COPPERTOXICITY
Prepared by: www.mcqsinpharmacology.com
 www.mcqsinpharmacology.com
COPPER
It is one of the first metals ever extracted
and it has made vital contributions to
sustaining and improving society since the
dawn of civilization.
It was first used in coins and ornaments
starting about 8000 B.C.
Around 5500 B.C., copper tools helped
civilization emerge from the Stone Age.
The discovery that copper alloyed with tin
produces bronze marked the beginning of
the Bronze Age at about 3000 B.C.
Daily intake of copper in adults varies between 0.9 and 2.2 mg, and
in children between 0.6 to 0.8 mg (WHO, 1998). It varies according
to age, pregnancy, and lactation.
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USES OF COPPER
It is an excellent conductor of electricity, as
such one of its main industrial usage is for
the production of cable, wire and electrical
products for both the electrical and building
industries.
The construction industry also accounts for
copper's second largest usage because it is
easily stretched, molded, and shaped. It is
also resistant to corrosion.
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Copper exposure in industry is primarily from inhaled
particulates in mining or metal fumes in smelting operations,
welding, or related activities.
Sanitary fittings
Insecticides and fungicides
Copper wire
Vitamin and mineral supplements (copper is an essential
micronutrient, but too much can be deadly).
Cookware.
Beverages containers
Stress
Birth control pills
SOURCES OF COPPER TOXICITY
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COPPER'S ROLE IN THE BODY
It has a number of important functions in the human body.
Bones and connective tissue. It is required to fix calcium in the
bones and to build and repair all connective tissue. Imbalances
can contribute to osteoporosis, and almost all conditions of the
skin, hair and nails.
Energy production in the cells. It is needed in the final steps of
the Krebs energy cycle called the electron transport system.
This is where most of our cellular energy is produced. Any
problem here causes fatigue, depression and other imbalances
related to low energy.
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Immune Response. It must remain in balance with zinc. When
imbalances occur, one is more prone to all infections, in
particular fungal and yeast infections.
The glandular system, particularly the thyroid and adrenal
glands. The thyroid gland is extremely sensitive to copper.
Common conditions seen with copper imbalance include
hypothyroidism and even hyperthyroidism. Grave’s disease
usually due to stress, copper imbalance and often mercury as
well.
Reproductive system. It is closely related to estrogen
metabolism, and is required for women's fertility and to maintain
pregnancy. Imbalance can cause premenstrual syndrome, ovarian
cysts, infertility, miscarriages, sexual dysfunctions and more. It
affects men less than women in this area, but it may affect men’s
potency and sexual drive.
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Nervous system. Copper stimulates production of the
neurotransmitters epinephrine, norepinephrine and dopamine.
Copper imbalances are highly associated with most
psychological, emotional and often neurological conditions.
These include memory loss, especially in young people,
depression, anxiety, bipolar disorder, and schizophrenia.
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TOXICITY MECHANISM
Stress cause the Stimulation of sympathetic nervous system which
release Adrenaline, Cortisol, and Aldosterone secretion.
Aldosterone work by retaining Na and Cu and increase the
elimination of Zn and Mg.
When the Adrenal glands are constantly being stimulated by
stress, the body retains Copper and eliminates Zinc. Zinc is
necessary for the removal of all toxic heavy metals including
Copper, and is also necessary for the production of
neurotransmitters in the brain.
When the brain starts becoming saturated with Copper but is
lacking the necessary neurotransmitters to calm the brain, the
mind becomes very agitated and is prone to severe mood swings.
Copper in Nervous System
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Copper must be bound to special binding proteins,
Ceruloplasmin and Metallothionine, in order to get into the
cells where it can be used by the Mitochondria to make ATP in
the Kreb's cycle. These proteins are made in the Liver upon
receiving a signal from the Adrenal glands to produce these
proteins.
If there is a dysfunction with either the Liver or the Adrenals than
these two proteins will be lacking and free and unbound Copper
will begin accumulating in the blood.
Copper and Blood
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Excess copper in the blood causes weakening of erythrocyte
membrane increasing there fragility leading to hemolysis.
Oxidation of hemoglobin by copper leads to methemoglobin,
which is unable to carry oxygen. This may aggravate the
hemolytic crisis.
Accumulation of copper occurs in mitochondria and lysosomes
cause hepatocyte damage leading to cellular degeneration or
necrosis.
Copper and Liver
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TOXICITY SYMPTOMS
Acne, Allergies, Hair loss,
Anemia, Anorexia, Anxiety,
Attention deficit disorder,
Arthritis, Autism, Candida
overgrowth, Dysmenorrhea,
Male infertility, Prostatitis,
Migraine, Headaches,
Insomnia, Neuralgia (nerve
pain), Sciatica Hypertension,
Hypothyroidism,
Schizophrenia, Bipolar
(Manic Depression) disorders.
www.mcqsinpharmacology.com
DIAGNOSIS
The hair copper level is a very unreliable indicator for copper
toxicity. So is serum copper, serum ceruloplasmin, and many
other tests because the copper can hide deep in the brain and the
liver.
A liver biopsy is a good indicator, but is a painful and somewhat
invasive procedure.
Hb Level Examination.
LFTs (AST, Lactate Dehydrgenase, Arginase, Sorbitol Dehydrogenase).
Serum or whole blood copper level.
www.mcqsinpharmacology.com
TREATMENT
Clinical improvement can be achieved by Chelation of
copper with d-penicillamine, Trien, zinc acetate, and
tetrathiomolybdate. The combination of
tetrathiomolybdate and zinc acetate is more effective.
N-Acetylcystein amide can cross the blood–brain barrier
And was developed to help prevent neurodegenerative
disorders.
www.mcqsinpharmacology.com
Hereditary Disease of Copper Metabolism
Menkes Disease: This is a rare sex-linked genetic defect in
copper metabolism resulting in copper deficiency in male infants.
It is characterized by peculiar hair, failure to thrive, severe metal
retardation, neurologic impairment, and death usually by 5 years
of age.
Wilson Disease: It is an autosomal recessive genetic disorder of
copper metabolism characterized by the excessive accumulation of
copper in liver, brain, kidneys, and cornea. Serum ceruloplasmin
is low and serum copper not bound to ceruloplasmin is elevated.
Urinary excretion of copper is high. Clinical abnormalities of the
nervous system.
www.mcqsinpharmacology.com
Indian Childhood Cirrhosis (ICC): This is a disorder occurring
in young children characterized by jaundice due to an insidious
and progressive liver disease. The etiology is not known but it is
suspected that bottle feeding of milk contaminated with copper
from storage in brass vessels may be important.
Idiopathic Copper Toxicosis or Non-Indian Childhood
Cirrhosis
This is a rare disorder in children similar to ICC occurring in
some western countries. The largest series of cases are reported
from Austria. This population also used copper vessels to store
milk, and the incidence of the disorder has declined since
replacement of the copper vessels. A number of other cases have
been reported from other parts of the world, some from increased
amounts of copper in drinking water.
www.mcqsinpharmacology.com

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COPPER TOXICITY: SYMPTOMS, CAUSES AND TREATMENT

  • 2. COPPER It is one of the first metals ever extracted and it has made vital contributions to sustaining and improving society since the dawn of civilization. It was first used in coins and ornaments starting about 8000 B.C. Around 5500 B.C., copper tools helped civilization emerge from the Stone Age. The discovery that copper alloyed with tin produces bronze marked the beginning of the Bronze Age at about 3000 B.C. Daily intake of copper in adults varies between 0.9 and 2.2 mg, and in children between 0.6 to 0.8 mg (WHO, 1998). It varies according to age, pregnancy, and lactation. www.mcqsinpharmacology.com
  • 3. USES OF COPPER It is an excellent conductor of electricity, as such one of its main industrial usage is for the production of cable, wire and electrical products for both the electrical and building industries. The construction industry also accounts for copper's second largest usage because it is easily stretched, molded, and shaped. It is also resistant to corrosion. www.mcqsinpharmacology.com
  • 4. Copper exposure in industry is primarily from inhaled particulates in mining or metal fumes in smelting operations, welding, or related activities. Sanitary fittings Insecticides and fungicides Copper wire Vitamin and mineral supplements (copper is an essential micronutrient, but too much can be deadly). Cookware. Beverages containers Stress Birth control pills SOURCES OF COPPER TOXICITY www.mcqsinpharmacology.com
  • 5. COPPER'S ROLE IN THE BODY It has a number of important functions in the human body. Bones and connective tissue. It is required to fix calcium in the bones and to build and repair all connective tissue. Imbalances can contribute to osteoporosis, and almost all conditions of the skin, hair and nails. Energy production in the cells. It is needed in the final steps of the Krebs energy cycle called the electron transport system. This is where most of our cellular energy is produced. Any problem here causes fatigue, depression and other imbalances related to low energy. www.mcqsinpharmacology.com
  • 6. Immune Response. It must remain in balance with zinc. When imbalances occur, one is more prone to all infections, in particular fungal and yeast infections. The glandular system, particularly the thyroid and adrenal glands. The thyroid gland is extremely sensitive to copper. Common conditions seen with copper imbalance include hypothyroidism and even hyperthyroidism. Grave’s disease usually due to stress, copper imbalance and often mercury as well. Reproductive system. It is closely related to estrogen metabolism, and is required for women's fertility and to maintain pregnancy. Imbalance can cause premenstrual syndrome, ovarian cysts, infertility, miscarriages, sexual dysfunctions and more. It affects men less than women in this area, but it may affect men’s potency and sexual drive. www.mcqsinpharmacology.com
  • 7. Nervous system. Copper stimulates production of the neurotransmitters epinephrine, norepinephrine and dopamine. Copper imbalances are highly associated with most psychological, emotional and often neurological conditions. These include memory loss, especially in young people, depression, anxiety, bipolar disorder, and schizophrenia. www.mcqsinpharmacology.com
  • 8. TOXICITY MECHANISM Stress cause the Stimulation of sympathetic nervous system which release Adrenaline, Cortisol, and Aldosterone secretion. Aldosterone work by retaining Na and Cu and increase the elimination of Zn and Mg. When the Adrenal glands are constantly being stimulated by stress, the body retains Copper and eliminates Zinc. Zinc is necessary for the removal of all toxic heavy metals including Copper, and is also necessary for the production of neurotransmitters in the brain. When the brain starts becoming saturated with Copper but is lacking the necessary neurotransmitters to calm the brain, the mind becomes very agitated and is prone to severe mood swings. Copper in Nervous System www.mcqsinpharmacology.com
  • 9. Copper must be bound to special binding proteins, Ceruloplasmin and Metallothionine, in order to get into the cells where it can be used by the Mitochondria to make ATP in the Kreb's cycle. These proteins are made in the Liver upon receiving a signal from the Adrenal glands to produce these proteins. If there is a dysfunction with either the Liver or the Adrenals than these two proteins will be lacking and free and unbound Copper will begin accumulating in the blood. Copper and Blood www.mcqsinpharmacology.com
  • 10. Excess copper in the blood causes weakening of erythrocyte membrane increasing there fragility leading to hemolysis. Oxidation of hemoglobin by copper leads to methemoglobin, which is unable to carry oxygen. This may aggravate the hemolytic crisis. Accumulation of copper occurs in mitochondria and lysosomes cause hepatocyte damage leading to cellular degeneration or necrosis. Copper and Liver www.mcqsinpharmacology.com
  • 11. TOXICITY SYMPTOMS Acne, Allergies, Hair loss, Anemia, Anorexia, Anxiety, Attention deficit disorder, Arthritis, Autism, Candida overgrowth, Dysmenorrhea, Male infertility, Prostatitis, Migraine, Headaches, Insomnia, Neuralgia (nerve pain), Sciatica Hypertension, Hypothyroidism, Schizophrenia, Bipolar (Manic Depression) disorders. www.mcqsinpharmacology.com
  • 12. DIAGNOSIS The hair copper level is a very unreliable indicator for copper toxicity. So is serum copper, serum ceruloplasmin, and many other tests because the copper can hide deep in the brain and the liver. A liver biopsy is a good indicator, but is a painful and somewhat invasive procedure. Hb Level Examination. LFTs (AST, Lactate Dehydrgenase, Arginase, Sorbitol Dehydrogenase). Serum or whole blood copper level. www.mcqsinpharmacology.com
  • 13. TREATMENT Clinical improvement can be achieved by Chelation of copper with d-penicillamine, Trien, zinc acetate, and tetrathiomolybdate. The combination of tetrathiomolybdate and zinc acetate is more effective. N-Acetylcystein amide can cross the blood–brain barrier And was developed to help prevent neurodegenerative disorders. www.mcqsinpharmacology.com
  • 14. Hereditary Disease of Copper Metabolism Menkes Disease: This is a rare sex-linked genetic defect in copper metabolism resulting in copper deficiency in male infants. It is characterized by peculiar hair, failure to thrive, severe metal retardation, neurologic impairment, and death usually by 5 years of age. Wilson Disease: It is an autosomal recessive genetic disorder of copper metabolism characterized by the excessive accumulation of copper in liver, brain, kidneys, and cornea. Serum ceruloplasmin is low and serum copper not bound to ceruloplasmin is elevated. Urinary excretion of copper is high. Clinical abnormalities of the nervous system. www.mcqsinpharmacology.com
  • 15. Indian Childhood Cirrhosis (ICC): This is a disorder occurring in young children characterized by jaundice due to an insidious and progressive liver disease. The etiology is not known but it is suspected that bottle feeding of milk contaminated with copper from storage in brass vessels may be important. Idiopathic Copper Toxicosis or Non-Indian Childhood Cirrhosis This is a rare disorder in children similar to ICC occurring in some western countries. The largest series of cases are reported from Austria. This population also used copper vessels to store milk, and the incidence of the disorder has declined since replacement of the copper vessels. A number of other cases have been reported from other parts of the world, some from increased amounts of copper in drinking water. www.mcqsinpharmacology.com