Ceruloplasmin within the normal range which means. Decreased blood levels. Causes of increased levels of ceruloplasmin
Ceruloplasmin is a protein produced in the liver. Responsible for the binding and transport of copper ions in the blood serum. Indeed, up to 90% of copper in the blood serum is present in the form associated with ceruloplasmin (one molecule binds 6-7 copper atoms). In addition, the protein, which is the main antioxidant in blood plasma, is responsible for 80% of the antioxidant properties.
The action of ceruloplasmin also lies in the oxidation of iron Fe2+ to Fe3+, which ensures its binding to transferrin and transport in the blood plasma. In addition, ceruloplasmin removes free radicals and activates the processes of oxidation of norepinephrine, serotonin, sulfidrylic compounds and ascorbic acid.
The study of the level of ceruloplasmin is not standard biochemical research blood. As a rule, it is ordered together with the study of the concentration of copper in the blood serum and the study of the daily excretion of copper in the urine. The indication for these studies is the suspicion that the patient has Wilson's disease.
Method for determining and norm of ceruloplasmin
Study ceruloplasmin concentrations carried out in case of suspected metabolic disorders copper ions especially if there is a suspicion Wilson's disease.
The concentration of ceruloplasmin is studied in serum venous blood. To do this, a blood sample is taken from a vein (usually from cubital vein), after which it is subjected to laboratory analysis. You must come to the study on an empty stomach (you should not take any food or drink 8 hours before blood loading). The result is usually expected one day.
Correct level of ceruloplasmin in adults it is 300-580 mmol / l, i.e. 30-58 mg / dl, and for infants up to 6 months of age, the norm is 240-540 mmol / l (24-145 mg / dl).
Interpretation of ceruloplasmin concentration results
A decrease in the concentration of ceruloplasmin in the blood serum below 200 mg / l occurs primarily in Wilson's disease. This disease is genetically determined and is associated with a defect in the protein that transports copper into hepatocytes, which, in turn, is determined by impaired synthesis of ceruloplasmin.
This leads to an excess of free (not bound to ceruloplasmin) copper in the blood serum and, at the same time, its excessive deposition in organs such as the liver, brain, and others. As a result, damage to these organs and the appearance of many non-specific diseases occur.
When liver damage- this is fatigue, nausea, lack of appetite, abdominal pain, jaundice. There are also neurological diseases similar to Parkinson's disease (tremor, difficulty walking, swallowing, speech), as well as epileptic seizures or migraine. Comes to the point of mental disorders such as personality change, psychosis, affective disorders.
A characteristic of Wilson's disease is the Kaiser and Fleischer ring, that is, a golden brown color around the cornea, associated with the deposition of copper there.
Note that a decrease in ceruloplasmin concentration does not necessarily indicate the onset of Wilson's disease, because this study is very error-sensitive and unreliable. Most often, simultaneously with the designation of the concentration of ceruloplasmin, they also study the concentration of copper in the blood serum (increase in the free fraction), the excretion of copper in the urine (more effective), and sometimes also evaluate the amount of copper in a liver biopsy (rarely). The performance of these tests, as well as the presence of characteristic clinical symptoms increases the likelihood of correct recognition of Wilson's disease.
An increase in the level of ceruloplasmin is also noted in pregnant women, women using hormonal contraception as well as in smokers. In addition, chronic inflammatory processes in the body and tissue necrosis can lead to increased synthesis of ceruloplasmin in the liver.
Method of determination Immunoturbidimetry.
Material under study Serum
First described in 1944 by Holmberg and Laurell. Ceruloplasmin is a protein of the plasma α2-globulin fraction, which contains about 95% total blood serum copper: one molecule of ceruloplasmin accounts for 6-8 copper atoms. High content copper gives it a blue color ("sky blue plasma protein"). Synthesized ceruloplasmin mainly parenchymal cells of the liver and, to a lesser extent, macrophages and lymphocytes. First, a peptide chain is formed, then copper is added from intracellular ATPase (the enzyme is absent in Wilson-Konovalov disease). The role of ceruloplasmin in the transport of copper itself is not very significant, since the turnover of copper in it is slow (the main role in the transport of copper is played by albumin and transcuprein).
As a biomarker of the state of copper metabolism in the body, ceruloplasmin is informative in conditions of its pronounced deficiency. The synthesis of ceruloplasmin is markedly stimulated by estrogens (pregnancy, estrogen therapy). Ceruloplasmin is an acute phase reactant. Its concentration in the blood increases during inflammation, infection, traumatic conditions- as a result of activation of transcription of the ceruloplasmin gene by α-interferon and cytokines. The rise in ceruloplasmin levels is relatively slow, peaking 4 to 20 days after an acute stroke.
Main physiological role ceruloplasmin is determined by its participation in redox reactions. Acting as a ferroxidase, ceruloplasmin performs essential role in the regulation of the ionic state of iron - the oxidation of Fe2+ to Fe3+. This makes it possible for iron to be incorporated into transferrin without the formation of toxic iron products. Maintaining normal iron transport and metabolism is vital important function ceruloplasmin. In iron deficiency, the transcription of the ceruloplasmin gene is activated by hypoxia-inducible factor-1 (HIF-1), which also activates the genes for erythropoietin, transferrin, and its receptor.
Ceruloplasmin may act as a pro-oxidant or as an antioxidant, depending on the presence of other factors. In the presence of superoxide (eg, in inflamed vascular endothelium), it catalyses the oxidation of low-density lipoproteins. Based on the results of epidemiological studies, ceruloplasmin is considered to be an independent risk factor for cardiovascular disease.
The primary genetic deficiency of ceruloplasmin in the homozygous form causes severe disorders of iron metabolism, in many respects similar to the picture of hemochromatosis. In this case, copper transport suffers to a lesser extent. Clinical picture includes blepharospasm, retinal degeneration, diabetes, dementia, extrapyramidal disorders. Secondary deficiency of ceruloplasmin (due to impaired incorporation of copper into its molecule during synthesis) is a much more frequent occurrence. Dietary copper deficiency (inadequate diet, parenteral nutrition, malabsorption, penicillamine therapy) is associated with neutropenia, thrombocytopenia, low serum iron, hypochromic normo- or macrocytic anemia refractory to iron therapy.
Menkes disease (“curly hair disease”) is an X-linked genetic anomaly disturbing copper receipts from gastrointestinal tract into the vascular space (there is no ATPase involved in the mechanisms of copper transport into the blood). Accordingly, copper does not enter the liver and is not available for inclusion in ceruloplasmin, its level is reduced. Clinically, the disease manifests itself in growth retardation, progressive neurological degeneration. Hair changes are characteristic (curly, sparse and brittle). Fatal outcome if untreated within the first 5 years of life.
Wilson-Konovalov's disease (hepatolenticular degeneration) is a defect in the gene of chromosome 13, leading to the absence of hepatic ATPase, which is involved in the mechanism of copper incorporation into ceruloplasmin, and the excretion of copper with bile is also impaired. Symptoms may appear in your 20s or 30s, but also earlier or later. Unlike ceruloplasmin deficiency associated with a copper-deficient diet and Menkes disease, in this condition there is an excess of copper in the body and its deposition in tissues, including the liver, brain, periphery of the iris (characteristic rings). Liver dysfunction develops, similar to acute or chronic hepatitis, degenerative changes CNS and neurological disorders, changes in kidney function, less often - hematological changes (hemolysis associated with toxic effect free copper). Excretion of copper in the urine increases 5-10 times. The level of ceruloplasmin is low (with the exception of occasional cases associated with pregnancy and inflammation).
Literature
Zaichik A. Sh., Churilov, L. P. Fundamentals of pathochemistry. - St. Petersburg: ELBI-SPb. 2001. - p. 417 - 418.
Radchenko V. G., Shabrov A. V., Zinovieva E. N. Fundamentals of clinical hepatology: diseases of the liver and biliary system. - M.: Dialect Binom, 2005. - 864 p.
Burtis C., Ashwood E., Bruns D. Tietz textbook of clinical chemistry and molecular diagnostics. Elsevir Inc., 2006. - 2412 p.
Martin F., Linden T., Katschinski D. M. et al. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood, 15 June 2005, vol. 105, no. 12, p. 4613 - 4619.
Fox P. L., Mazumder B., Ehrenwald E., Mukhopadhyay C. K. Ceruloplasmin and cardiovascular disease. Free Radic Biol Med. Jun 15 2000, 28(12), p. 1735-44.
> Determination of the content of ceruloplasmin in the blood
This information cannot be used for self-treatment!
Be sure to consult with a specialist!
Ceruloplasmin is a unique protein in the human body that contains copper. Copper is absorbed with food digestive tract and enters the liver, where it binds to apoceruloplasmin, forming ceruloplasmin.
The main task of this protein is to ensure the processes of oxidation and reduction of iron. Due to this, iron is converted into the form in which it can be incorporated into transferrin and hemoglobin. Main clinical significance analysis for ceruloplasmin consists in assessing the metabolism of copper, which suffers in some congenital diseases, for example, in Wilson-Konovalov disease.
Who can prescribe a blood test for ceruloplasmin, where can it be taken?
Pediatricians, hematologists, rheumatologists, therapists can prescribe this analysis. You can donate blood for this indicator in a biochemical laboratory or in a specialized department where the patient is being examined or treated.
In what situation is the blood tested for ceruloplasmin?
This study is a screening test in the diagnosis of Wilson's disease - Konovalov and others. genetic diseases leading to disorders of copper metabolism (Menkes disease). In dynamics, the indicator is determined to assess the quality of treatment of these diseases.
The following complaints may serve as the reason for referral for analysis: tremor and decreased muscle tone, fatigue, growth retardation, anemia, difficulty swallowing. specific symptom, speaking in favor of Wilson's disease - Konovalov, are Fleischer rings (rims Brown color near the irises).
Normal levels of ceruloplasmin in the blood, and how the results are interpreted
In blood healthy person the content of this protein is 220–610 mg/l. An increase is noted at inflammatory diseases(maximum by 4-20 days of illness), with Hodgkin's disease, rheumatoid arthritis, liver diseases ( obstructive jaundice, hepatitis). In pregnant women in the third trimester, the content of ceruloplasmin may double, which is physiological norm. Reception of some medicines(phenytoin, oral contraceptives) can lead to a temporary increase in the concentration of ceruloplasmin in the blood.
A low concentration of this protein is recorded in Wilson-Konovalov disease, curly hair syndrome (Menkes disease). Low content copper in food, for example, when parenteral nutrition, leads to a decrease in the index.
Advantages and disadvantages, clinical significance of the ceruloplasmin study
The main advantage of this analysis is that it is used as a screening study in the diagnosis of Wilson's disease - Konovalov. At the same time, its use does not guarantee 100% diagnostic accuracy, since in a small percentage of people with this disease, the indicator remains normal even if there are clinical symptoms. In this regard, it is necessary to additional definition copper concentrations in blood and urine.
The purpose of this analysis is relevant for assessing the quality of therapy for diseases that occur with impaired copper metabolism. In this case, research on initial stages diseases are carried out every two weeks with gradual increase interval up to 1–1.5 months. Since most of the drugs used to treat this pathology are quite toxic, it is advisable to prescribe together with a blood test for ceruloplasmin general analysis blood and tests to determine functional state liver.
Study Information
ceruloplasmin- copper-containing protein (glycoprotein) present in blood plasma. Ceruloplasmin contains about 95% of the total amount of copper in human blood serum. Ceruloplasmin performs a number of important functions in the body. biological functions: increases stability cell membranes, participates in immunological reactions (in the formation defensive forces body), ion exchange, has an antioxidant (preventing lipid peroxidation of cell membranes) effect, stimulates hematopoiesis (hematopoiesis).
Raise concentration of ceruloplasmin observed in patients with acute and chronic infectious diseases, liver cirrhosis, hepatitis, myocardial infarction, systemic diseases, lymphogranulomatosis, in patients with schizophrenia. The content of ceruloplasmin in the blood serum also increases with malignant neoplasms different localization (lung cancer, breast, cervix, gastrointestinal tract) by 1.5 - 2 times, reaching more significant values with the prevalence of the process. Successful chemo and radiation treatment accompanied by a decrease in the level of ceuloplasmin up to normal level. With inefficiency combination therapy, as well as with the progression of the disease, the content of ceruloplasmin remains high.
Failure ceruloplasmin due to a violation of its synthesis in the liver causes Konovalov-Wilson disease ( hereditary disease liver, associated with a violation of the metabolism of proteins and copper), which is an important diagnostic indicator. Low levels Serum ceruloplasmin levels are also observed in nephrotic syndrome, diseases of the gastrointestinal tract, serious illnesses liver.
Special training research is not required. Need to follow general requirements preparation for research.
GENERAL RULES:
1. For most studies, it is recommended to donate blood in the morning, from 8 to 11 am, on an empty stomach (at least 8 hours should elapse between the last meal and blood sampling, you can drink water as usual), the day before research easy restricted dinner fatty foods. For infection tests and emergency investigations, it is acceptable to donate blood 4-6 hours after the last meal.
2.ATTENTION! Special rules for preparing for a number of tests: strictly on an empty stomach, after 12-14 hours of fasting, you should donate blood for gastrin-17, lipid profile(total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, lipoprotein (a), apolipo-proten A1, apolipoprotein B); a glucose tolerance test is performed in the morning on an empty stomach after 12-16 hours of fasting.
3. On the eve of the study (within 24 hours), exclude alcohol, intense physical exercise, taking medications (as agreed with the doctor).
4. 1-2 hours before donating blood, refrain from smoking, do not drink juice, tea, coffee, you can drink non-carbonated water. Exclude physical stress(running, fast climbing stairs), emotional arousal. It is recommended to rest and calm down 15 minutes before donating blood.
5. You should not donate blood for laboratory research immediately after physiotherapy procedures, instrumental examination, X-ray and ultrasound research, massage and other medical procedures.
6. Under control laboratory indicators in dynamics, it is recommended to conduct repeated studies in same conditions- in the same laboratory, donate blood at the same time of day, etc.
7. Blood for research should be donated before the start of taking medications or no earlier than 10-14 days after they are discontinued. To evaluate the control of the effectiveness of treatment with any drugs, it is necessary to conduct a study 7-14 days after the last dose of the drug.
If you are taking medication, be sure to tell your doctor about it.
What is Ceruloplasmin in the blood and what is its rate I will consider further in detail. It is a metalloglycoprotein, a sky-blue plasma protein unique color arises due to high content in the body of copper, in the exchange of which it participates. The biosynthesis of this protein is carried out in the liver, directly in hepatocytes, which are liver cells, and the synthesis of this substance can also take place in lymphocytes, in addition, in macrophages.
The norm of ceruloplasmin in a healthy person in bloodstream usually has a stable value, which varies from 150.0 to 600 mg / liter, but with pathological process These figures can change both up and down. In newborns, this is not the norm and this figure is two times less. An exception may be pregnant women, as well as the fair sex, who use oral drugs at their own discretion. contraceptives.
An increase in the level of ceruloplasmin when it happens?
Elevated levels of ceruloplasmin can be provoked hormonal influence, namely the amount of estrogen produced. Ceruloplasmin includes a copper molecule and interacts with plasma proteins. It increases the stability of cell membranes; has an anti-inflammatory effect; participates in the regulation of the transition of the divalent form of iron to the original ferric iron; stimulates blood formation; provides production of hemoglobin; ceruloplasmin has a powerful antioxidant effect.
A change in activity in one direction or another of ceruloplasmin is associated with a shift in the concentration of copper ions in the bloodstream. An increase in this indicator can be observed in the following situations: chronic processes; necrotic tissue damage; myocardial infarction; hematological pathology; malignant processes; acute dysentery; liver disease; nonspecific pneumonia; collagenoses; melanoma; pernicious anemia; in addition, schizophrenia; as well as a long history of smoking can also cause an increase in this parameter.
Decrease in the level of ceruloplasmin when it happens?
ceruloplasmin is lowered by following states: violation of its production in the liver tissue; in severe Konovalov-Wilson disease, when a person has hepatocerebral degeneration, usually accompanied by congenital disorder copper exchange.
In addition, the level of ceruloplasmin decreases in other conditions: with identified nephrotic syndrome; with pathology of the gastrointestinal tract (with enteropathy, when protein loss is noted, in addition, with malabsorption syndrome); with severe liver pathology, when normal biosynthesis of ceruloplasmin by hepatocytes is impossible.
In addition to these situations, a decrease in the ceruloplasmin parameter occurs in Menkes syndrome, when curly hair syndrome is noted; with hypochromic microcytic anemia; with insufficient copper-containing protein of a hereditary nature; with an insufficient amount of copper in the products used.
With a diagnosed deficiency of ceruloplasmin, copper ions begin to leave the bloodstream and, so to speak, "walk" in the extravascular space. At the same time, they pass through the kidneys, partially removed with urine (the concentration of copper in the urine is increased), or they accumulate in connective tissue fibers (for example, in the cornea of the eye).
Of extreme importance in terms of the manifestation of symptoms of a pathological condition is the parameter of copper accumulation directly in the central nervous system in its structures. AT similar situation concentration of copper in the blood falls. As a result, the body suffers, since the accumulated copper ions disrupt the activity of many systems and the most important organs.
The parameters of ceruloplasmin in the blood should correspond to the above norm, but if the level of this protein is slightly increased or decreased, then this may indicate the presence in the body of any pathological conditions. Which must be identified with the help of appropriate diagnostics and prescribed to the patient therapeutic measures aimed at normalizing well-being.
