Myoglobinuria

When myoglobin is detected in the urinary fluid, doctors diagnose myoglobinuria. For the vast majority of patients this term is incomprehensible, and even suspicious. What is myoglobinuria concealing, and is it worth being afraid of this condition?

Myoglobin refers to the pigmentary protein substance that is part of the cellular structure of the muscles. It is considered as a banal respiratory pigment component responsible for the temporary reserve of oxygen in the muscle tissue. Myoglobin takes part in the intracellular transport of oxygen.

Before the onset of myoglobinuria, another condition is usually found - myoglobinemia.

[1], [2], [3],

Epidemiology

Myoglobinuria is considered a relatively rare condition. For a hundred thousand people, the risk of developing the disease is present in 6-8 people.

Young people develop mainly myoglobinuria of hereditary type. If the disease affects people after 30 years, then in a similar situation it is necessary to look for other reasons that in some cases can not be identified.

[4], [5], [6], [7],

Causes of the myoglobinuria

Hereditary-family pathologies:

1. with the clarified mechanism of the anomaly (Mc-Ardl's syndrome, TARUI syndrome, deficiency of carnitine palmityltransferase);
2. with unknown primary anomaly (malignant form of hyperthermia, lactic acid synthesis disorder, abnormal oxidation of fatty acids);
3. congenital variant of myopathy on the background of an additional factor - anesthesia (muscular dystrophy Shi and Meji, Duchenne myopathy, chondrodystrophic myotonia).

Acquired pathologies:

1. changes associated with a mechanical disorder (trauma, heart attack, ischemia);
2. hyper load on the musculature (overload of untrained muscles, lifting of heavy objects, epistatus, psychosis, electric shock);
3. feverish conditions (intoxications, infections, etc.);
4. infection without fever (influenza, tetanus, diseases that are accompanied by acidosis and a violation of the electrolyte balance);
5. inflammatory processes, poisoning, intoxication.

Disease with an unclear reason.

[8], [9], [10]

Risk factors

The provoking factors in myoglobinuria may include:

• physical hyper-effort;
• excessive muscle tension;
• limited intake of carbohydrates into the body;
• inflammatory diseases of the muscle tissue;
• mechanical damage to muscle tissue (trauma, crash syndrome, positional compression syndrome);
• overtraining;
• current exposure;
• intoxication (medicinal, alcoholic, etc.).

Myoglobinuria can develop in people with alcohol dependence, as well as those who smoke more packets of cigarettes every day. In a similar situation, pathology arises from the toxic effects of ethyl alcohol, carbon monoxide and nicotine gums.

The disease often affects fans of cocaine, heroin, amphetamine, and also observed after bites of snakes, scorpions, poisonous spiders, after poisoning with mushrooms.

[11], [12], [13], [14], [15], [16], [17], [18]

Pathogenesis

The pathogenesis of different types of myoglobinuria has much in common. Expressed destructive processes in the musculature, regardless of the underlying cause of the disease, provoke the release of myoglobins. By comparison, one muscle loses about 75% of pigment and 65% of potassium.

Myoglobin has a small molecular weight, in contrast to hemoglobin (respectively, 16-20 thousand and 64.5 thousand). Due to this, myoglobin is 25 times more likely to overcome the filtration system and appears in the urinary fluid during the first day after excretion from the tissues. In an acidic environment, myoglobin is able to precipitate to form acid hematin - this causes clogging of the ascending segment of the renal loops (Henle).

Myoglobin toxic: accumulating in distant areas of renal structural units, it provokes myoglobinuric nephrosis and, as a consequence, acute tubular necrotic process. Kidneys also suffer from other toxic metabolic products, as well as potassium - the plasma content of potassium in soft tissue damage increases to 7-11 mmol. The hemodynamic processes inside the kidneys are disrupted, the tubular inverse absorption of water and sodium is increased, since mass release of the antidiuretic hormone occurs along with aldosterone. The listed moments in the complex affect the further development of acute kidney failure.

[19], [20], [21],

Symptoms of the myoglobinuria

Symptomatology in myoglobinuria is far from the same in all cases: it depends on the concentration of myoglobin and the presence of concomitant pathological disorders. Most patients complain of sudden strong weakness, tenderness in the muscles, heaviness in the lumbar region, bouts of nausea. The volume of secreted urinary fluid is sharply and greatly reduced - the development of anuria is not excluded. Attention is drawn to the change in the color of urine. Thus, the first signs of myoglobinuria consist in the fact that the urinary fluid becomes saturated red to saturate brown, until blackening.

The benzidine test is positive. The specific gravity of urine gradually decreases, proteinuria is detected. The urine sediment contains cylinders, hematin, erythrocytes.

If further acute renal failure develops, then signs of general intoxication develop, azotemia, hyperkalemia, and acidosis are observed.

Stages

Isolate stage I - up to 2 days after cessation of compression. This stage is called the period of local changes and internal intoxication. For this period are characteristic: pain in the injured limb, impaired motor function, increasing edema, "hardening" of the muscles, blue skin, weakness, nausea, blood pressure drop, dizziness. Other typical symptoms are myoglobinemia, increased blood clotting properties, increased levels of potassium and phosphorus, and a decrease in the amount of urine. In the urinary fluid is determined protein, cylinders, the color changes to dark brown. If at this stage there is qualitative medical care (including surgical), then there is a short "enlightenment" in the form of symptomatology. However, further there is a sharp deterioration, which is the second stage of myoglobinuria - an acute failure of renal activity, which can last 3-12 days.

During the II stage, the puffiness progresses, intradermal blisters and hematomas appear. The liquefaction of blood replaces hemodilution, anemia increases, the excretion of the urinary fluid stops completely. This period especially often ends in a lethal outcome - in about 35% of cases.

Stage III - recovery - begins with a favorable outcome of the previous stage, when the renal function stabilizes, the level of proteins and electrolytes in the bloodstream comes back to normal. This period is no less dangerous: development of infectious complications, septic conditions is not ruled out.

[22], [23], [24], [25], [26], [27], [28]

Forms

Myoglobinuria is divided into several varieties:

• Paroxysmal myoglobinuria, which is characterized by myalgia, sudden general and muscle weakness, muscle paralysis, fever, abdominal pain, brown-red intense color of the urinary fluid.
• Idiopathic myoglobinuria, which is characterized by the development of necrotic processes in the muscles, nephronecrosis, insufficient kidney function, acute myoglobinous myositis and muscle porphyria (due to disturbance of porphyrin metabolic processes).
• Traumatic myoglobinuria, typical of the syndrome of "crushing" (crash syndrome). It begins with a sudden darkening of the urinary fluid (for 2-3 hours from the moment of traumatization), against the background of the existing crushing and necrosis of the damaged muscles (the so-called "fish meat" type).
• Postobic myoglobinuria is a consequence of thermal and electrical burns that are large in size and depth (in terms of symptoms it has much in common with a traumatic type of pathology).
• Obturation myoglobinuria is associated with acute arterial obstruction, vascular obturation and, as a consequence, acute muscular ischemia.
• Toxic alimentary myoglobinuria occurs when fish products are used from certain water bodies (for example, Yuksovskoe lake).
• Marching myoglobinuria develops after excessive physical exertion on the musculature. Especially often this happens during sports, namely: with intense walking or running, with long climbing, during skiing or biking, swimming. There is a development of traumatic myositis, cell membranes are damaged. Myoglobinuria in athletes is manifested by severe pain in the muscles, swelling in the affected musculature, convulsions, fever, increased ESR, leukocytosis, impaired liver and kidney function.

[29], [30]

Complications and consequences

Complications of myoglobinuria are not uncommon if the patient does not receive the necessary medical care, or his address to the doctor becomes belated. In this situation, we can talk about the only possible consequence - a severe kidney failure, the result of which is the development of coma and death.

To avoid these consequences, medical care is provided as soon as possible - that is, immediately.

[31], [32], [33], [34], [35], [36],

Diagnostics of the myoglobinuria

The doctor sets the diagnosis, paying attention to the characteristic clinical picture, given the presence of trauma or pathology, which could lead to the appearance of myoglobinuria. Additionally, there are tests for the presence of myoglobin in the blood and urinary fluid. In order to identify myoglobin, different techniques are used using capillary electrophoresis (starch gel or paper test), Blondheim's test and spectrophotometry.

Myoglobin refers to muscle pigments, and its chemical structure is similar to hemoglobin. Using standard chemical tests for blood will not help distinguish one protein from another. Therefore, specific instrumental diagnostics are used for identification. Electrophoresis on paper is used to determine the muscle pigments in serum and urinary fluid. As reagents, 3% sulfosalicylic acid and crystalline ammonium sulfate are used. Take 1 ml of urine, mix 3 ml of sulfosalicylic acid, filter and centrifuge. If a red-brown precipitate eventually forms, it means that the urine contains any of the protein pigments. In order to clarify what kind of pigment in question, in 5 ml of urinary fluid dilute 2.8 g of ammonium sulfate. A positive reaction is indicated if the concentration of myoglobin is not less than 30-40 mg%.

[37], [38], [39], [40], [41]

Differential diagnosis

Differential diagnosis is conducted between myoglobinuria and hemoglobinuria :

	Myoglobinuria	Hemoglobinuria
Staining of plasma	Does not stain	Stained
Appearance in the urine	Almost immediately	Later
Staining of urine	Brownish-brown color	Cherry red color ("meat slops")
Precipitation of urine in  I day	Does not contain shaped elements	From the first day contains red blood cells, pigmented cylinders, hemosiderin
The presence of hemosiderin	Absent	Present

Treatment of the myoglobinuria

Myoglobinuria is treated only by qualified specialists under hospital conditions, with constant monitoring of the electrolyte balance state.

The main emphasis in therapy is placed on the prompt cleansing of the patient's blood from toxic substances that are formed as a result of the decomposition of myocytes. This purification is performed against the background of stabilization of the functionality of the urinary system.

The main medical measures are:

1. The strictest bed rest.
2. Introduction of rehydration solutions for elimination of toxic substances.
3. The introduction of diuretic drugs for getting rid of puffiness (Furosemide, Mannitol).
4. Carrying out blood transfusion (with intravascular coagulation syndrome).
5. Dialysis in the development of acute kidney failure (to prevent coma).
6. If necessary, surgical treatment (if necrosis of muscle fibers is present).
7. The introduction of analgesics from the group of opium (non-steroidal anti-inflammatory drugs are not used in any case).
8. Dietary (sometimes parenteral) meals with an emphasis on proteins and potassium.
9. Ensure that sufficient fluids enter the body.

After stabilizing the patient's condition, he can be transferred to outpatient treatment.

Medications

To stabilize blood circulation, to prevent the development of shock and acute kidney failure in myoglobinuria, infusion treatment is performed. At the same time, diuresis and central venous pressure indices are constantly monitored.

In order to detoxify and speed up recovery, salt preparations, glucose solution 5%, isotonic sodium chloride solution, albumin, frozen plasma are introduced. To optimize microcirculatory processes, rheopolyglucin and heparin (5 thousand units) are used.

To compensate for metabolic acidosis, intravenously drip a solution of sodium bicarbonate (4%). If necessary, antibacterial drugs are used in the form of intramuscular injections.

Much attention is paid to symptomatic treatment of myoglobinuria, which may include the use of diuretics, analgesics, antihistamines and cardiac drugs.

With crash syndrome, it is appropriate to perform early extracorporeal hemocorrection - hemodialysis, hemosorption, plasmosorption, plasmapheresis.

Vitamins

At the stage of recovery to the general course of treatment necessarily include vitamins.

• Cyanocobalamin (B ₁₂ ) - improves the metabolism of carbohydrates, supports the nervous system, stimulates the restoration of muscles, provides adequate reduction, development and coordination of muscles.
• Biotin - is involved in amino acid metabolism and provides energy potential.
• Riboflavin (B ₂ ) - is involved in the metabolism of proteins, the oxidation of fatty acids, the metabolism of glucose.
• Retinol (A) - is involved in the synthesis of protein and the production of glycogen, providing normal muscle growth.
• Tocopherol (E) is an antioxidant that protects cell membranes, which promotes the growth of myocytes and restores muscle tissue.
• Vitamin D - is necessary for the assimilation of phosphorus and calcium, which are necessary to ensure normal muscle contractility.
• Pyridoxine (B ₆ ) - provides a normal exchange of proteins and the utilization of carbohydrates.
• Ascorbic acid - accelerates the regeneration and growth of myocytes, takes part in the formation of collagen, improves the assimilation of iron.

Physiotherapeutic treatment

Physiotherapy in myoglobinuria is not used.

After the surgical intervention at a remote stage, a rehabilitative therapy is prescribed, which includes massage procedures, physical therapy - first of all, to restore the function of damaged muscles and get rid of contractures.

Alternative treatment

Treatment with alternative agents in the period of acute symptoms of myoglobinuria is not welcomed, as this can lead to aggravation of the condition and acceleration of the development of complications. Such treatment can be used only at the stage of rehabilitation, to restore the body after myoglobinuria, but only against the background of other medical appointments.

You can use these alternative recipes:

• Take 1 tsp. Finely chopped pomegranate peel and 200 ml of boiling water. The skin is poured with boiling water and insisted for a couple of hours, filtered. Drink 1 tbsp. L. Three times a day before meals.
• Take half a kilogram of apples of green varieties, 100 g of pumpkin pulp, a couple of sprigs of mint, 2 tbsp. L. Sugar, boiling water. Apples are washed and cleaned, cut into cubes and placed in a container. Pour in the same 1 st. L. Sugar, put mint, add 500 ml of boiling water and boil on low heat for 45 minutes. Drain the formed liquid into another container, knead the boiled apples to a puree state. Pumpkin is cleaned and cut, add 1 tbsp. L. Sugar, pour 1 liter of boiling water and boil on low heat for an hour. Next, the water is drained and cooked from pumpkin puree.

Combine two kinds of mashed potatoes, pour liquid from apples, mix well. Store in the refrigerator, taking 3 tablespoons. L. Three times a day for half an hour before a meal.

• Prepare the compote of sea-buckthorn berries, hips, several lobes of lemon. Lemon can be added to the finished product, as well as honey - for sweets. Compote drink 100 ml three times a day for 20 minutes before meals.
• Pour 500 liters of oats with one liter of boiling water, insist 40 minutes, filter. Infusion drink 100 ml three times a day before meals.

Alternative treatment, unfortunately, will not replace medical prescriptions. It should be remembered that myoglobinuria is a condition requiring urgent medical attention, so any experiments with self-medication can lead to extremely negative consequences.

[42], [43], [44], [45], [46], [47], [48]

Herbal Treatment

At the stage of rehabilitation after consultation with the doctor, you can apply the treatment of medicinal plants.

• Prepare an infusion of 1 tbsp. L. Violet color, 1 tbsp. L. Flowers celandine, 1 tsp. St. John's wort, 1 tbsp. L. Rhizomes of dandelion and 500 ml of water. The product is poured with boiling water and insisted for an hour. Filter and drink a quarter cup three times a day for 30 minutes before meals. Duration of treatment - 4 weeks.
• Pour 1 tbsp. L. Of wild cherry fruit 200 ml of boiling water, boil on low heat for 20 minutes, after which it is filtered. Drink a quarter cup to 4 times a day, regardless of meals.
• Prepare the infusion of 200 g of parsley leaves, 100 g of oregano, 50 g of cucumbers and 1.5 liters of boiling water. After 40 minutes the infusion is filtered, 1 tsp is added. Salt, stir. Drink a quarter of a glass after each meal.

Homeopathy

At the stage of rehabilitation after myoglobinuria, the use of certain homeopathic remedies is allowed:

• Adrenaline - stabilizes blood pressure, reduces the severity of pain;
• Aurum muriatikum - improves diuresis and triggers mechanisms of adaptation in the body;
• Hamomilla - improves motor function, eliminates spasms and cramps, normalizes sleep;
• Gelzemium - eliminates nausea, trembling in the limbs, cramps, normalizes motor activity;
• Kali muriatikum - helps with delusional disorders, normalizes the excretion of urine;
• Opium - normalizes sleep, lowers reflex excitability, improves urination;
• Solidoga - cleanses the blood of toxic substances.

It is not necessary to take homeopathic remedies alone, it is better to contact a homeopathic doctor who will help to choose the right drug and its dosage.

Surgery

Operative treatment may consist of:

• Fasciotomy, which helps to eliminate strong compression of tissues;
• correction of fractures, which can aggravate the situation;
• operations on the removal of dead tissue.

The need for surgical treatment, as well as the scale of the operation, is determined individually by the attending physician.

Fasciotomy is performed if the viability of the musculature is preserved, but subfascial edema is expressed against the background of disturbed local blood flow. The operation involves the revision and excision of dead muscle bundles. In the absence of purulent discharge, the wound is sutured for 3-4 days. This is possible if the puffiness subsides, and the overall well-being of the patient tends to improve.

If there is persistent ischemia, then the only way out is amputation of the limb above the site of the applied bundle.

In other situations, excision of dead tissue with reconstruction of viable muscles is performed. Evaluation of viability is possible only during surgery. If the muscle has a normal color, is capable of bleeding and contracting, then it is recognized as capable of further existence. Excision is completed by thoroughly washing the tissues with antiseptic solutions. There is no need for suturing: the wound surface is tightened by secondary tension.

Prevention

Preventive measures to prevent the development of acute renal failure in the background of a traumatic type of myoglobinuria consist in the timely removal of dead tissue (sometimes completely remove the damaged limb).

When providing first aid, local cooling procedures are of considerable preventative value. If the extremities are damaged, a tourniquet should be applied.

For the prevention of non-traumatic myoglobinuria, it is necessary to adequately treat the underlying pathology; patients with marsh myoglobinuria should limit walking time and avoid physical exertion.

General recommendations for the prevention of pathology may be as follows:

• It is impossible to ignore any injuries that are accompanied by damage to the musculature;
• during physical exertion, during the treatment of infectious diseases, after receiving injuries should be given enough attention to compliance with the drinking regime - that is, to drink clean water in the quantities necessary for the body;
• The intensity of the sports load must be controlled and corrected, avoiding overloading;
• should abandon alcohol, smoking, drugs;
• under no circumstances should you allow self-treatment of injuries and infectious diseases.

If the patient, by force of circumstances, can not move for a certain time (for example, after an injury), then he should do special dosage exercises to prevent the blood from stagnating in the tissues. Such exercises are developed and controlled by the attending physician.

[49], [50], [51], [52], [53]

Forecast

The prognosis depends entirely on the course of the underlying pathology and on the degree of damage to the kidney structures. If the patient develops a failure of renal activity and anuria, then the probability of a fatal outcome is high.

Non-traumatic myoglobinuria differs in a relatively favorable prognosis, but it is difficult to talk about a positive outcome in the development of myoglobinuric myositis.

[54], [55], [56], [57]

Useful links

• Myoglobinuria https://en.wikipedia.org/wiki/Myoglobinuria
• Myoglobinuria: Background, Pathophysiology, Epidemiology https://emedicine.medscape.com/article/982711-overview
• Myoglobinuria https://www.ncbi.nlm.nih.gov/pubmed/10658177
• Myoglobinuria, Hemoglobinuria, and Acute Renal Failure https://pdfs.semanticscholar.org/ffae/3570df6a4117b5877e0a585fbaceda4b756a.pdf

[58],