CLINICAL SYMPTOMS AND MANAGEMENT OF COPPER POISONING.pptx

Copper toxicity occurs when there is an excessive accumulation of copper in the body, which can lead to various health issues.Chronic copper toxicity is the hallmark of Wilson’s disease, an autosomal recessive genetic disorder in which there is deficiency of ceruloplasmin.

1. CLINICAL SYMPTOMS OF ACUTE AND CHRONIC MANAGEMENT OF COPPER POISONING S.REKHA ASSOCIATE PROFESSOR, EGSCOP.

2. Introduction: Copper toxicity occurs when there is an excessive accumulation of copper in the body, which can lead to various health issues. Copper is an essential trace mineral that supports vital functions like enzyme activity, iron metabolism, and nerve function. Copper has a crystalline structure that greatly influences its physical properties. Atomic Number : 29 : Symbol :cu Copper is a highly versatile and widely used metal known for its distinctive reddish-brown color

3. Some examples of copper salts include:  Copper sulfate : An inorganic compound that is used as a fungicide. It is created by treating cupric oxide with sulfuric acid. Copper sulfate forms large, bright blue crystals. When heated, the blue salt turns white.  Blue vitriol Copper(II) chloride :  CuCl2.  Copper(II) hydroxide :  Cu(OH)2 .  Copper(II ) nitrate :  Cu(NO3)2 .  Copper acetate:   Cu ( OAc ) 2 Coppersubacetoarsenite: Cu(C2H3O2)2·3Cu(AsO2)2

4. Applications: Electrical Wiring : Due to its high electrical conductivity. Plumbing : Resists corrosion and is easy to work with. Construction : Roofing, cladding, and decorative elements. Industrial : Heat exchangers, bearings, and seals. Medical : Touch surfaces in hospitals for its antimicrobial properties. Coins : Used in currency due to its durability. Copper’s unique combination of properties makes it essential in a wide range of industries and everyday applications.

5. Benefits of Copper: Copper is crucial for various biological functions, including: Enzyme Function : Acts as a cofactor for enzymes involved in energy production, iron metabolism, and neurotransmitter synthesis. Examples include cytochrome c oxidase (energy production) and ceruloplasmin (iron transport). Iron Absorption and Transport : Helps convert iron into its usable form for hemoglobin production, preventing anemia.

6. Connective Tissue Formation : Supports the cross-linking of collagen and elastin, maintaining the strength of bones, skin, and blood vessels. Immune System : Enhances immune defense by supporting white blood cell activity. Brain and Nervous System : Aids in the synthesis of neurotransmitters, contributing to brain health and function. Antioxidant Properties : Participates in neutralizing free radicals, reducing oxidative stress.

7. Sources of Copper Copper is found in a variety of foods, including: Animal Sources : Shellfish, liver, and organ meats. Plant Sources : Nuts, seeds, legumes, whole grains, and leafy greens. Other Sources : Drinking water from copper pipes and certain dietary supplements.

8. Daily Recommended Intake The amount of copper needed depends on age, gender, and life stage: Infants (0-12 months) : 200-220 µg/day Children (1-8 years) : 340-440 µg/day Adolescents (9-18 years) : 700-890 µg/day Adults (19+ years) : 900 µg/day Pregnancy and Lactation : 1,000-1,300 µg/day

9. Copper Deficiency: Although rare, copper deficiency can lead to: Anemia (due to impaired iron absorption). Weakened Immune System . Bone Abnormalities (osteoporosis or fractures). Neurological Issues (difficulty walking, numbness, or fatigue). Cardiovascular Problems .

10. Causes of Copper Toxicity: Excessive Intake : Overuse of copper supplements. High levels of copper in drinking water (e.g., from corroded copper pipes). Occupational Exposure : Workers in mining, welding, or manufacturing industries may be exposed to excessive copper. Liver Dysfunction : Impaired liver function reduces the body's ability to excrete copper properly. Environmental Factors : Ingestion of contaminated food or exposure to copper-containing pesticides and fungicides.

11. Chronic inhalation of copper sulfate spray used as an insecticide in vineyards can cause vineyard sprayer’s lung disease characterised by a histiocytic granulomatous lung. Chronic contact with swimming pool water containing algicidal copper chemicals can cause green hair discoloration. Cooking in copper or brass vessels can cause copper poisoning due to verdigris. Copper poisoning can also result from the leaching of copper containers in which carbonated water, citrus fruit juices, and other acidic beverages have been stored . Dyspnoea has developed after oral copper exposure. Skin exposure can produce severe irritation, itching, erythema , dermatitis and eczema.

12. Chronic copper toxicity is the hallmark of Wilson’s disease , an autosomal recessive genetic disorder in which there is deficiency of ceruloplasmin . Discoloration of the peripheral part of the cornea (Kayser-Fleischer ring) is a feature of this condition characterised by deposition of copper in parenchymal tissue . A ‘sunflower-like ’ discoloration of the most anterior layers of the lens has also been reported in patients with Wilson’s disease. Metal fume fever, wheezing and rales have been reported in workers exposed to fine copper dust.

13. Toxicokinetics : Absorption:  Copper is absorbed through skin, GIT, lungs and mucous membrane . Distribution: Normally copper is bound in the blood to ceruloplasmin (95%) and albumin. Organs with a high copper content include the liver, brain, heart and kidneys. However, excess copper can accumulate in almost every organ of the body. Metabolism: Main site of metabolism is liver. In the hepatocyte, copper may either be incorporated into enzymes and form metallothionein -copper complex in biliary-system. Elimination: It is excreted through bile and traces are found in saliva and milk. Renal excretion is negligible.

14. Toxicity mechanism: Copper in Nervous System Stress causes 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.  

15. Copper and blood: 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 Krebs'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.

16. Copper and Liver 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.

17. Fatal dose: 10-20gms of CuSo4 or copper sub acetate Fatal period:12-24 hrs or delayed for week

18. Acute Signs and Symptoms of Copper Toxicity: Large amount of copper is ingested, inhaled, or absorbed over a short period 1. Gastrointestinal Symptoms Nausea and Vomiting : Often the first symptoms; may include vomiting with a green or bluish tint (indicative of copper salts). Abdominal Pain & Diarrhoea. 2. Systemic Symptoms Headache : Due to systemic toxicity and dehydration. Metallic Taste : A distinct coppery taste in the mouth is a hallmark of acute exposure. Dizziness and Weakness : Resulting from dehydration and systemic effects. 3. Hepatic (Liver) Symptoms Jaundice : Yellowing of the skin and eyes due to liver dysfunction. Elevated Liver Enzymes : Indicates liver damage.

19. 4. Cardiovascular Symptoms Hypotension &Tachycardia 5. Renal (Kidney) Symptoms Oliguria : Reduced urine output due to kidney damage. Hematuria : Presence of blood in the urine. 6. Neurological Symptoms Confusion and Irritability : Resulting from systemic toxicity. Seizures : In severe cases of toxicity. 7. Respiratory Symptoms (if Inhaled) Irritation : Of the throat and nasal passages. Difficulty Breathing : In cases of severe inhalation exposure. 8. Severe Cases Shock : Due to severe fluid loss, low blood pressure, and organ failure. Coma : In extreme cases, untreated acute toxicity can lead to loss of consciousness.

20. Chronic Signs and Symptoms of Copper Toxicity: Chronic copper toxicity occurs due to prolonged exposure to elevated levels of copper, often accumulating over time in the liver, brain, and other organs. 1. General Symptoms: Fatigue : Persistent tiredness due to metabolic and oxidative stress. Weakness : A generalized feeling of reduced physical strength. Loss of Appetite : Often accompanied by unexplained weight loss. 2. Liver Symptoms Jaundice : Yellowing of the skin and eyes, indicating liver damage. Abdominal Discomfort : Due to liver inflammation or enlargement. Hepatic Encephalopathy : Confusion or altered mental status caused by severe liver dysfunction.

21. 3. Neurological Symptoms Mood Changes : Depression, irritability, or anxiety. Cognitive Impairment : Difficulty concentrating, memory issues, or mental fog. Tremors or Movement Disorders : Similar to Parkinsonism in severe cases. Headaches : Frequent and persistent. 4. Gastrointestinal Symptoms Recurrent Nausea and Vomiting : May occur periodically. Diarrhea : Occasional or persistent. Abdominal Pain : Diffuse or localized, depending on the extent of organ involvement. 5. Kidney Symptoms Hematuria : Blood in the urine due to kidney damage. Proteinuria : Presence of protein in urine, indicating nephropathy. Reduced Kidney Function : Gradual decline leading to symptoms like swelling or electrolyte imbalances.

22. 6. Cardiovascular Symptoms Hypertension : Elevated blood pressure due to vascular damage. Arrhythmias : Irregular heartbeats in severe cases. 7. Skin and Hair Symptoms Grayish or Pale Skin : Due to anemia from copper’s interference with iron metabolism. Brittle Hair : Weakening of hair strands. Dark Rings Around the Eyes (Kayser-Fleischer Rings) : Due to copper deposits in the cornea, a hallmark of Wilson’s disease. G reen line gums at the base of teeth.

23. 8. Immune System Symptoms Infections : Reduced immunity due to impaired white blood cell function. Chronic Inflammation : Low-grade systemic inflammation. 9. Reproductive Symptoms Menstrual Irregularities : Disrupted cycles or amenorrhea in women. Reduced Fertility : In both men and women

24. Investigations for Copper Toxicity 1. Laboratory Tests Serum Copper Levels: Elevated copper levels in the blood indicate acute or chronic exposure. Normal range: 70–140 µg/ dL . Interpretation: High levels: Acute or chronic copper overload. Low levels with symptoms: May suggest Wilson’s disease (copper accumulates in tissues, reducing free serum levels). Serum Ceruloplasmin: Ceruloplasmin is a copper-binding protein produced by the liver. Normal range: 20–35 mg/ dL . Interpretation: Low levels (<20 mg/ dL ): Seen in Wilson’s disease or severe liver dysfunction. Normal or high levels: May indicate non-genetic copper overload Urinary Copper Excretion: Elevated urinary copper is a marker of copper toxicity. Normal range: <50 µg/24 hours .

25. Liver Function Tests (LFTs): (AST, ALT) indicate liver damage from copper accumulation. Complete Blood Count (CBC): Hemolysis Markers: Lactate Dehydrogenase (LDH) : Elevated due to hemolysis. Haptoglobin : Low in hemolysis. 2. Genetic Testing Performed if Wilson’s disease is suspected. Detects mutations in the ATP7B gene , which regulates copper transport and excretion.

26. 3. Imaging Studies Liver Biopsy: Used to measure copper content directly in liver tissue. Copper levels >250 µg/g dry weight are diagnostic for copper overload. MRI or CT Scans: Detect structural or functional changes in the liver and brain. Useful for assessing damage from chronic copper accumulation (e.g., basal ganglia changes in Wilson’s disease). Ophthalmologic Examination: Slit-Lamp Examination : Identifies Kayser -Fleischer rings , copper deposits in the cornea, commonly seen in Wilson’s disease.

27. Management of Copper Toxicity The management of copper toxicity aims to reduce copper levels in the body, address symptoms, and prevent complications. Treatment strategies depend on whether the toxicity is acute or chronic. 1. Acute Copper Toxicity Acute copper toxicity is a medical emergency caused by ingesting, inhaling, or absorbing a large amount of copper in a short period. Immediate Steps: Identify and Remove the Source : Stop further exposure to contaminated water, food, or occupational sources.

28. Stabilize the Patient : Address life-threatening symptoms like dehydration, electrolyte imbalances, or shock. Intravenous (IV) fluids to restore hydration and maintain blood pressure. Gastrointestinal Decontamination : Stomach wash : 1% K ferrocyanide (which reacts with copper sulphate to give insoluble cupric ferrocyanide) Albumin: to form copper albuminate (insoluble) Activated Charcoal : May help reduce copper absorption in the gastrointestinal tract

29. Chelation Therapy: Chelation agents bind excess copper, facilitating its excretion: Penicillamine : First-line chelating agent. Dose: 1–1.5 g/day in divided doses. Side effects: Nausea, rash, and potential bone marrow suppression. Trientine : Alternative for patients intolerant to penicillamine . Better-tolerated with fewer side effects. .

30. Supportive Care: Antiemetic's : For nausea and vomiting. Pain Management : For abdominal cramps. Monitoring : Liver and kidney function. Electrolyte levels and blood pressure. 2. Chronic Copper Toxicity Chronic copper toxicity develops over time due to prolonged exposure or genetic conditions like Wilson's disease . Dietary Adjustments: Reduce intake of copper-rich foods:

31. Shellfish, liver, nuts, seeds, and chocolate. Avoid cooking with unlined copper utensils. Chelation Therapy: Penicillamine : Commonly used for Wilson’s disease and chronic copper overload. Trientine : Effective alternative, particularly for long-term management. Zinc Therapy: Zinc Acetate : Blocks copper absorption in the gut. Dose: 50 mg three times daily.

32. Liver Support: In cases of significant liver damage: Antioxidants : May help protect liver cells. Liver Transplant : Considered for advanced liver failure (e.g., cirrhosis due to Wilson’s disease). Neurological and Psychiatric Management: Address movement disorders, depression, or anxiety associated with copper buildup in the brain. Physical therapy for neurological symptoms.

33. 3. Monitoring and Follow-Up Regular Laboratory Tests : Serum copper and ceruloplasmin levels. Urinary copper excretion. Liver and kidney function tests. Eye Exams : Monitor for Kayser-Fleischer rings in Wilson's disease. Genetic Counseling : For patients and families with Wilson’s disease or other genetic predispositions.

34. 4. Preventive Measures Test Drinking Water : Especially in areas with older plumbing systems. Copper concentrations in water should be <1.3 ppm (EPA guidelines). Workplace Safety : Use protective equipment in industries with potential copper exposure. Avoid Unnecessary Supplements : Avoid taking copper-containing supplements unless prescribed.

35. Autopsy Features: 1. Jaundiced skin and conjunctivae. 2. Greenish or bluish stomach contents. 3. Hepatic and renal necrosis. Forensic Issues: In India, the incidence of suicidal ingestion of copper sulfate was quite high till recently. Of late, there has been a decline.

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