Clinical Relevance and Management of Copper Related Disorders
Abstract: Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.

"Nervous System...Abnormal copper transport or aberrant copper-protein interactions may have a role in the development of neurodegenerative diseases. Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, and Prion diseases all have misfolded proteins that form inclusion bodies involving copper linked processes [33]...

Cardiovascular System...Copper deficiency in the cardiovascular system can contribute to hypertension, anemia, coagulation abnormalities, and arteriosclerosis. In animal models dietary deficiency (<1 mg Cu/kg) leads to severe morphological and functional changes. Concentric cardiac enlargement, ventricular aneurysms, mitochondrial disruption, distorted myocytes, and altered proportions of contractile proteins have been documented....Copper deficiency leads to morphological changes in the vascular system including altered connective tissue composition and tensile strength leading to aneurysm formation. Vasoactivity of both large and small vessels is altered contributing to derangement in blood pressure homeostasis. Impairment of antioxidant defenses may play a role in development of atherogenesis and ischemic heart disease...

Immune System...Reduced ATPase7A expression attenuates macrophage bactericidal activity and may in part explain the increased susceptibility to respiratory tract infections commonly reported in patients with Menkes disease...

Hematopoietic System...Coagulation and fibrinolysis are both affected by copper deficiency. Clot formation is delayed; however, thrombi grow more rapidly and lyse more slowly. Copper deficiency impairs endothelial platelet adhesion, enhances platelet aggregation, and delays time to thrombus initiation. Bleeding time is increased and growth phase of the thrombus reduced...

Endocrine System...Copper induced oxidative stress may contribute to the development of both diabetes and its complications. Advanced glycation end products (AGEs), formed by spontaneous nonenzymatic chemical reactions between carbohydrates and tissue proteins, are one proposed mechanism for the development of diabetic lesions. AGEs accumulate in the vascular, kidney, extra cellular matrix (ECM), and basement membranes. Complications may result from modifications of existing protein structure and function, interaction with AGE specific receptors, and generation of ROS. Accumulation of catalytically active Cu2+ binding AGEs in long lived ECM proteins may mediate local oxidative stress leading to tissue damage...

Copper and Pregnancy...Copper plays an important role in normal pregnancy and embryogenesis. Serum copper increases early in pregnancy reaching levels at term approximately twice those of nonpregnant women. Lower plasma copper levels have been found in some conditions diagnosed during the first trimester including spontaneous, threatened and missed abortion, and blighted ovum. Serum and placental copper levels and placental lipid peroxides, a marker of oxidative stress, were found to be increased in women with severe preeclampsia [71]. Impaired placental copper trafficking may also play a role in the development of placental insufficiency through reduced expression of ATP7A [72].
Excessive copper is teratogenic and has been associated with fetal intrauterine growth restriction and neurological sequelae. Small amounts from intrauterine devices can prevent embryogenesis by blocking implantation and blastocyst development [73]. Patients with untreated Wilson’s disease often have spontaneous abortions but there are no consistent reports of fetal abnormalities. Chronic liver disease and resulting hormonal changes may also lead to infertility [74]. Serum copper levels are reportedly higher in women with a history of post partum depression (PPD) compared to nonpregnant women with depression; raising the possibility of using elevated serum copper as a potential marker to identify women with a predisposition to PPD.....
http://www.hindawi.com/journals/arp/2013/750901/


Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders
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Anesthesiology Research and Practice is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of anesthesiology.