Trace element : Copper

D i.e. Hepatocellular carcinoma 

– Copper is excreted in the bile into GI tract from which it is not reabsorbed. So normally urine contains only traces of copper. Since copper homeostasis is maintained almost exclusively by biliary excretionQ, any disease which hampers its biliary excretion will lead to accumulation of Cu in liver —> increased blood levels & increased urinary excrition. So cholestatic hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis show increased copper excretion in urineQ.

Wilson disease has defect in copper binding P type ATPase (ATP 7B protein) which cause defective excretion of copper into bile & reduction in incorporation of copper into apoceruloplasmin 1/t accumulation of Cu in liver, brain, kidney & RBC.

Ans. is ‘a’ i.e., Ceruloplasmin

o Normally, 40% to 60% of daily ingested copper (2 to 5 mg) is absorbed in the stomach & duodenum. o It is transported to the liver loosely complexed with albumin.

o Free copper dissociates and is taken up into hepatocytes, where it is incorporated into an 0(₂-globulin synthesized in

the endoplasmic reticulum to form ceruloplasmin (a copper-containing metallothionein) and resecreted into plasma. o Ceruloplasmin accounts for 90% to 95% of plasma copper, although its biologic role is unknown, since the six to

seven atoms of copper in each protein molecule are not readily exchangeable.

o Circulating ceruloplasmin is desialylated as part of normal plasma protein aging

o Desialylated ceruloplasmin is endocytosed by the liver, degraded within lysosomes, and its copper is excreted into bile. This degradation/excretion pathway is the primary route for copper elimination.

o Estimated total body copper is only 50 to 150 mg.

C i.e. Copper

B i.e. 1 – 3 days

B i.e. Copper poisoning

– Average fatal period of copper salt (15 gm sub acetate/ 30gm sulfate) poisoning is 1-3 daysQ

– Blue green (or purple-green) pigmentation of hair, skin, mucosa and perspiration, purple (blue) green line on gumsQ and bluish green frothy discharge from mouth and nostrilsQ is seen in chronic poisoning of copper salt.

D i.e. Copper Sulphate

Ans. is ‘d’ i.e., Keshan disease

Keshan disease is a disorder of selenium metabolism.

o Following diseases are related to copper metabolism :-

i)         Wilson’s disease

ii)         Menkes kinky hair syndrome

Indian childhood cirrhosis (increased hepatic, urinary and serum copper concentration are characteristic of ICC).

Ans. is ‘None’ 

Answer is B (Copper deficiency)

Cu deficiency has not been mentioned to cause megaloblastic picture. It causes a normocytic hypochromic picture.

• Orotic acid is an intermediate metabolite in the synthesis of pyrimidines. Orototic aciduria is a rare disorder in children, resulting from block of further metabolism of orotic acid.

Affected children have megaloblastic anemia that is unresponsive to Vit C, Vit B12 and folic acid.

• Thiamine deficienc^y may be associated with ‘thiamine responsive anemia’. In the untreated state this gives rise to a megaloblastic anemia. –

Liver disease may give rise to megaloblastic anemia, by interferring with storage and metabolism of fat soluble vitamin B

Causes of Macrocytic anemia

1. Vit. B_it deficiency
2. Folic acid deficiency
3. Orotic aciduria
4. Nitrous oxide inhalation
5. Liver disease
6. Hypothyroidism
7. Thiamine deficiency

Ans. Copper

Ans. C: Copper

A deposit of fine particles of copper in the lungs or other tissues is known as chalcosis.

Ans. A i.e. Renal failure

Ans. B: Potassium ferrocyanide

Treatment of copper poisoning:

• Stomach wash with 1 percent solution of potassium ferrocyanide which acts as an antidote by forming an insoluble cupric ferrocyanide
• Emetics are contraindicated
• Demulcent drinks form insoluble albuminate of copper
• Castor oil
• Chelation with penicillamine/ EDTA/ BAL

Ans. Penicillamine

Ans. Copper sulfate

Ans. Acute hemolysis

Ans. A and C both

Ans. is ‘d’ i.e., Ceruloplasmin

Ans. is ‘a’ i.e., Ceruloplasmin

Copper is mainly transported as ceruloplasmin :‑

• Normally, 40% to 60% of daily ingested copper (2 to 5 mg) is absorbed in the stomach & duodenum. o It is transported to the liver loosely complexed with albumin.
• Free copper dissociates and is taken up into hepatocytes, where it is incorporated into an a_,-globulin synthesized in the endoplasmic reticulum to form ceruloplasmin (a copper-containing metallothionein) and resecreted into plasma.
• Ceruloplasmin accounts for 90% to 95% of plasma copper, although its biologic role is unknown, since the six to seven atoms of copper in each protein molecule are not readily exchangeable.
• Circulating ceruloplasmin is desialylated as part of normal plasma protein aging
• Desialylated ceruloplasmin is endocytosed by the liver, degraded within lysosomes, and its copper is excreted into bile. This degradation/excretion pathway is the primary route for copper elimination.
• Estimated total body copper is only 50 to 150 mg.

Ans. is ‘b’ i.e., Impaired copper transport

Menke’s disease is caused due to defect in the copper transport.

• There is defect in the transport of copper present in the intestinal mucosa to the blood stream.
• The mucosal lining of intestine contains high level of copper bound to metallothionein protein.
• Rather than being transporated to bloodstream, the copper remained in the mucosa and was lost when intestinal cells were naturally soughed off.

Menkes disease is caused due to defect in the “MNK” gene.

• The protein normally function by moving copper from the intestinal mucosal cells into the blood stream, where it is hound by proteins such as albumin and transported to organs and tissues.

Serum copper is critical for the functioning of several enzymes

Lysyl oxidase             →        It is important for the cross linking of collagen and elastin such that deficiencies lead to problems in connective tissues such as bones

Cytochrome oxidase  →         Involved in temperature maintenance

Tyrosinase                →         Necessary for pigmentation

Clinical features of menkes disease

• Growth retardation
• Coarse hair, brittle and ivory white (result of depigmentations). The hair fibres are twiisted and broken helically (kinky hair).
• Seizures
• Cerebral and cerebellar degeneration (postmortem analysis)
• Hypothermia
• Thrombosis
• Poor bone development
• Increased tendency towards aneurysms

Ans. b. Copper poisoning