Myoglobinuria

When myoglobin is detected in urine, doctors diagnose myoglobinuria. For the vast majority of patients, this term is incomprehensible and even suspicious. What does myoglobinuria hide, and should we be afraid of this condition?

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

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

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Epidemiology

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

Young people are mostly affected by hereditary myoglobinuria. If the disease affects people after 30 years of age, then in such a situation it is necessary to look for other causes, which in some cases cannot be identified.

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Causes myoglobinuria

Hereditary familial pathologies:

1. with an identified mechanism of the anomaly (McArdle syndrome, Tarui syndrome, carnitine palmityltransferase deficiency);
2. with unknown primary anomaly (malignant hyperthermia, lactic acid synthesis disorder, abnormal fatty acid oxidation);
3. congenital variant of myopathy against the background of an additional factor - anesthesia (congenital muscular dystrophy Shi and Medzhi, Duchenne myopathy, chondrodystrophic myotonia).

Acquired pathologies:

1. changes associated with mechanical disturbance (trauma, infarction, ischemia);
2. hyperstrain of muscles (overload of untrained muscles, lifting heavy objects, epileptic status, psychosis, electric shock);
3. febrile conditions (intoxication, infections, etc.);
4. infections without fever (flu, tetanus, diseases accompanied by acidosis and electrolyte imbalance);
5. inflammatory processes, poisoning, intoxication.

Disease of unknown cause.

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Risk factors

Provoking factors for myoglobinuria may include:

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

Myoglobinuria can develop in people suffering from alcohol addiction, as well as in those who smoke more than a pack of cigarettes daily. In such a situation, the pathology occurs as a result of the toxic effects of ethyl alcohol, carbon monoxide and nicotine resins.

The disease often affects cocaine, heroin, and amphetamine users, and is also observed after snake bites, scorpions, poisonous spiders, and mushroom poisoning.

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Pathogenesis

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

Myoglobin has a low molecular weight, unlike hemoglobin (respectively, 16-20 thousand and 64.5 thousand). Due to this, myoglobin overcomes the filtering system 25 times faster and ends up in the urine during the first day after being removed from the tissues. In an acidic environment, myoglobin can precipitate with the formation of acidic hematin - this causes blockage of the ascending segment of the renal loops (Henle).

Myoglobin is toxic: accumulating in the distant parts of the renal structural units, it provokes myoglobinuric nephrosis and, as a consequence, acute tubular necrotic process. The kidneys also suffer under the influence of other toxic metabolic products, as well as potassium - the plasma potassium content increases to 7-11 mmol when soft tissues are damaged. Hemodynamic processes inside the kidneys are disrupted, tubular reabsorption of water and sodium increases, since there is a massive release of antidiuretic hormone along with aldosterone. The listed factors in combination affect the further development of acute renal failure.

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Symptoms myoglobinuria

The symptoms of myoglobinuria are not the same in all cases: it depends on the concentration of myoglobin and the presence of concomitant pathological disorders. Most patients complain of sudden severe weakness, muscle pain, heaviness in the lumbar region, and bouts of nausea. The volume of excreted urine decreases sharply and greatly - the development of anuria is also possible. Noteworthy is the change in the color of urine. Thus, the first signs of myoglobinuria are that the urine becomes from deep red to deep brown, up to blackening.

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

If acute renal failure develops later, signs of general intoxication increase, azotemia, hyperkalemia, and acidosis are observed.

Stages

Stage I is distinguished - up to 2 days after the compression stops. This stage is called the period of local changes and internal intoxication. This period is characterized by: pain in the injured limb, impaired motor function, increasing edema, "petrification" of muscles, blue skin, weakness, nausea, a drop in blood pressure, dizziness. Other typical symptoms are myoglobinemia, increased clotting properties of the blood, increased levels of potassium and phosphorus, and a decrease in the amount of urine. Protein, cylinders are detected in the urine, the color changes to dark brown. If high-quality medical care is provided at this stage (including surgical care), then a short-term "clarification" is observed in the form of a decrease in symptoms. However, then a sharp deterioration occurs, which is stage II of myoglobinuria - this is acute renal failure, which can last 3-12 days.

During stage II, the swelling progresses, intradermal blisters and hematomas appear. Blood liquefaction is replaced by hemodilution, anemia increases, and the excretion of urine stops completely. This period is especially often fatal – in about 35% of cases.

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

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Forms

Myoglobinuria is divided into several types:

• Paroxysmal myoglobinuria, which is characterized by myalgia, sudden general and muscle weakness, muscle paralysis, fever, abdominal pain, and rich brown-red color of urine.
• Idiopathic myoglobinuria, which is characterized by the development of necrotic processes in the muscles, nephronecrosis, insufficient renal function, acute myoglobinuric myositis and muscular porphyria (due to a violation of porphyrin metabolic processes).
• Traumatic myoglobinuria, typical for the "crush syndrome". It begins with a sudden darkening of the urine (within 2-3 hours from the moment of injury), against the background of existing crushing and necrosis of the damaged muscles (the so-called "fish meat" appearance).
• Post-burn myoglobinuria is a consequence of large and deep thermal or electrical burns (in terms of symptoms, it has much in common with the traumatic type of pathology).
• Obstructive myoglobinuria is associated with acute arterial obstruction, vascular obstruction and, as a consequence, acute muscle ischemia.
• Toxic alimentary myoglobinuria occurs when consuming fish products from certain bodies of water (for example, Lake Yuksovskoye).
• March myoglobinuria develops after excessive physical exertion on the muscles. This happens especially often during sports, namely: during intensive walking or running, during long climbs, during skiing or cycling races, swimming. The development of traumatic myositis is observed, cell membranes are damaged. Myoglobinuria in athletes is manifested by severe muscle pain, swelling in the area of the affected muscles, cramps, fever, increased ESR, leukocytosis, impaired liver and kidney function.

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Complications and consequences

Complications of myoglobinuria are not uncommon if the patient does not receive the necessary medical care or if his visit to the doctor is too late. In such a situation, we can talk about the only possible consequence - severe renal failure, the result of which is the development of a comatose state and death.

To avoid the above-mentioned consequences, medical assistance is provided as early as possible – that is, immediately.

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Diagnostics myoglobinuria

The doctor establishes a diagnosis by paying attention to the characteristic clinical picture, taking into account the presence of trauma or pathology that could lead to the appearance of myoglobinuria. In addition, tests are carried out for the presence of myoglobin in the blood and urine. In order to identify myoglobin, various methods are used using capillary electrophoresis (starch gel or paper test), Blondheim test and spectrophotometry.

Myoglobin is a muscle pigment, and its chemical structure is similar to hemoglobin. Standard chemical tests for blood will not help to distinguish one protein from another. Therefore, specific instrumental diagnostics are used for identification. Paper electrophoresis is used to determine muscle pigments in serum and urine. 3% sulfosalicylic acid and crystalline ammonium sulfate are used as reagents. Take 1 ml of urine, add 3 ml of sulfosalicylic acid, filter and centrifuge. If a red-brown sediment forms as a result, this means that the urine contains one of the protein pigments. In order to clarify which pigment is in question, 2.8 g of ammonium sulfate is diluted in 5 ml of urine. A positive reaction is said to occur if the concentration content of myoglobin is at least 30-40 mg%.

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Differential diagnosis

Differential diagnosis is made between myoglobinuria and hemoglobinuria:

	Myoglobinuria	Hemoglobinuria
Plasma staining	Not painted	It is being painted
Appearance in urine	Almost immediately	Later
Urine coloring	Brownish-brown color	Cherry red color ("meat slops")
Urine sediment on day 1	Does not contain any formed elements	From the first day it contains erythrocytes, pigment cylinders, hemosiderin
Presence of hemosiderin	Absent	Present

Treatment myoglobinuria

Treatment of myoglobinuria is carried out only by qualified specialists in a hospital setting, with constant monitoring of the electrolyte balance.

The main focus of therapy is on the fastest possible purification of the patient's blood from toxic substances that form as a result of the breakdown of myocytes. Such purification is carried out against the background of stabilization of the functionality of the urinary system.

The main treatment measures are:

1. Strict bed rest.
2. Introduction of rehydration solutions to remove toxic substances.
3. Administration of diuretics to relieve swelling (Furosemide, Mannitol).
4. Carrying out blood transfusion (in case of intravascular coagulation syndrome).
5. Conducting dialysis in the development of acute renal failure (to prevent coma).
6. If necessary, surgical treatment (if there is necrosis of muscle fibers).
7. Administration of painkillers from the opium group (non-steroidal anti-inflammatory drugs are not used under any circumstances).
8. Dietary (sometimes parenteral) nutrition with an emphasis on proteins and potassium.
9. Ensuring that the body receives sufficient amounts of fluid.

Once the patient's condition has stabilized, he or she can be transferred to outpatient treatment.

Medicines

Infusion therapy is performed to stabilize blood circulation, prevent the development of shock and acute renal failure in myoglobinuria. Diuresis and central venous pressure indicators are simultaneously and constantly monitored.

For the purpose of detoxification and acceleration of recovery, saline preparations, 5% glucose solution, isotonic sodium chloride solution, albumin, frozen plasma are administered. Rheopolyglucin and heparin (5 thousand U) are used to optimize microcirculatory processes.

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

Much attention is also paid to the symptomatic treatment of myoglobinuria, which may include taking diuretics, painkillers, antihistamines and cardiac medications.

In case of crush syndrome, it is appropriate to perform early extracorporeal hemocorrection – hemodialysis, hemosorption, plasmasorption, plasmapheresis.

Vitamins

At the recovery stage, vitamins are necessarily added to the general course of treatment.

• Cyanocobalamin (B ₁₂ ) – improves carbohydrate metabolism, supports the nervous system, stimulates muscle recovery, ensures adequate contraction, development and coordination of muscles.
• Biotin – participates in amino acid metabolism and provides energy potential.
• Riboflavin (B ₂ ) – participates in protein metabolism, oxidation of fatty acids, and glucose metabolism.
• Retinol (A) – participates in protein synthesis and glycogen production, ensuring normal muscle growth.
• Tocopherol (E) is an antioxidant that protects cell membranes, promotes myocyte growth and restores muscle tissue.
• Vitamin D is needed for the absorption of phosphorus and calcium, which are necessary to ensure normal muscle contractility.
• Pyridoxine (B ₆ ) – ensures normal protein metabolism and carbohydrate utilization.
• Ascorbic acid – accelerates the regeneration and growth of myocytes, participates in the formation of collagen, improves the absorption of iron.

Physiotherapy treatment

Physiotherapy is not used for myoglobinuria.

After surgery, rehabilitation therapy is prescribed at a late stage, including massage procedures and therapeutic exercise - primarily to restore the function of damaged muscles and get rid of contractures.

Folk remedies

Treatment with folk remedies during the period of acute symptoms of myoglobinuria is not welcomed, as this can lead to a worsening of the condition and acceleration of the development of complications. Such treatment is allowed to be used only at the rehabilitation stage, to restore the body after myoglobinuria, but only against the background of other medical prescriptions.

The use of the following folk recipes is permitted:

• Take 1 teaspoon of finely chopped pomegranate peel and 200 ml of boiling water. Pour boiling water over the peel and leave for a couple of hours, filter. Drink 1 tablespoon three times a day before meals.
• Take half a kilogram of green apples, 100 g of pumpkin pulp, a couple of sprigs of mint, 2 tbsp. of granulated sugar, boiling water. Wash and peel the apples, cut into cubes and place in a container. Pour in 1 tbsp. of granulated sugar, put in the mint, add 500 ml of boiling water and boil over low heat for 45 minutes. Drain the resulting liquid into another container, mash the boiled apples until puree-like. Peel and chop the pumpkin, add 1 tbsp. of granulated sugar, pour in 1 liter of boiling water and boil over low heat for an hour. Then drain the water and make pumpkin puree.

Combine the two types of puree, pour in the liquid from the apples, and mix well. Store in the refrigerator, taking 3 tablespoons three times a day half an hour before meals.

• Prepare a compote from sea buckthorn berries, rose hips, and a few lemon slices. Lemon can be added to the finished product, as well as honey – for sweetness. Drink 100 ml of compote three times a day 20 minutes before meals.
• Pour one liter of boiling water over 500 g of oats, leave for 40 minutes, filter. Drink 100 ml of the infusion three times a day before meals.

Folk remedies, unfortunately, will not replace medical prescriptions. It is important to remember that myoglobinuria is a condition that requires immediate medical intervention, so any experiments with self-medication can lead to extremely negative consequences.

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Herbal treatment

At the rehabilitation stage, after consultation with a doctor, treatment with medicinal plants can be used.

• Prepare an infusion of 1 tbsp. violet flowers, 1 tbsp. celandine flowers, 1 tsp. St. John's wort, 1 tbsp. dandelion rhizome and 500 ml of water. Pour boiling water over the remedy and leave for an hour. Filter and drink a quarter of a glass three times a day 30 minutes before meals. Duration of treatment is 4 weeks.
• Pour 1 tbsp. of bird cherry fruits with 200 ml of boiling water, simmer over low heat for 20 minutes, then filter. Drink a quarter of a glass up to 4 times a day, regardless of meals.
• Prepare an infusion of 200 g of parsley leaves, 100 g of oregano, 50 g of immortelle and 1.5 l of boiling water. After 40 minutes, filter the infusion, add 1 teaspoon of salt and stir. Drink a quarter of a glass after each meal.

Homeopathy

At the stage of rehabilitation after myoglobinuria, the use of individual homeopathic remedies is permitted:

• Adrenaline – stabilizes blood pressure, reduces the severity of pain;
• Aurum muriaticum – improves diuresis and triggers adaptation mechanisms in the body;
• Chamomilla – improves motor function, eliminates spasms and cramps, normalizes sleep;
• Gelsemium – eliminates nausea, tremors in the limbs, convulsions, normalizes motor activity;
• Kali muriaticum – helps with delusional disorders, normalizes urine excretion;
• Opium – normalizes sleep, reduces reflex excitability, improves urination;
• Solidago - cleanses the blood of toxic substances.

You should not take homeopathic remedies on your own; it is better to consult a homeopathic doctor who will help you choose the right drug and its dosage.

Surgical treatment

Surgical treatment may include:

• fasciotomy, which helps to eliminate severe tissue compression;
• correction of fractures that may aggravate the situation;
• operations to remove dead tissue.

The need for surgical treatment, as well as the scale of the operation, is determined by the attending physician on an individual basis.

Fasciotomy is performed if the viability of the muscles is preserved, but there is pronounced subfascial edema against the background of impaired local blood flow. The operation includes revision and excision of dead muscle bundles. In the absence of purulent discharge, the wound is sutured on the 3rd-4th day. This is possible if the swelling subsides and the patient's general well-being tends to improve.

If there is persistent ischemia, then the only solution is amputation of the limb above the area of the applied tourniquet.

In other situations, excision of dead tissue with reconstruction of viable muscles is performed. Viability can only be assessed during surgery. If the muscle has a normal color, is able to bleed and contract, it is considered capable of further existence. Excision is completed by thorough washing of the tissue with antiseptic solutions. There is no need to apply sutures: the wound surface is tightened by secondary intention.

Prevention

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

When providing first aid, local cooling procedures are of considerable preventive importance. In case of damage to the extremities, it is necessary to apply a tourniquet.

To prevent non-traumatic myoglobinuria, it is necessary to adequately treat the underlying pathology; patients with march myoglobinuria should limit walking time and avoid physical activity.

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

• Any injuries that involve muscle damage should not be ignored;
• during physical activity, during treatment of infectious diseases, after receiving injuries, you should pay sufficient attention to maintaining a drinking regimen - that is, drink clean water in the volumes necessary for the body;
• the intensity of the sports load must be kept under control and adjusted, avoiding overload;
• you should give up alcohol, smoking, and drugs;
• Under no circumstances should self-treatment of injuries and infectious diseases be allowed.

If the patient is unable to move for a certain period of time due to circumstances (for example, after an injury), then he should do special dosed exercises to prevent blood stagnation in the tissues. Such exercises are developed and monitored by the attending physician.

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Forecast

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

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

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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

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