Myopathy-nephropathy metabolic syndrome

　　One, Etiology

　　7. Acute arterial obstruction

　　(1) Acute arterial embolism.

　　(2) Non-occlusive arterial obstruction. Including: ①Acute thrombosis of the abdominal aorta or abdominal aortic aneurysm; ②Femoral artery catheterization during extracorporeal circulation; ③Arterial trauma; ④Blood flow blockage by clamping during aortic reconstruction.

　　4. Ischemic muscle necrosis.

　　3. Non-traumatic myopathy, long-term coma, drug toxicity, infection, burn, metal poisoning.

　　Two, Pathogenesis

　　1. Within a few hours after acute arterial obstruction, the affected limb may present pallor and edema. This change is more pronounced at 24 hours. At this time, cutting through the muscle may reveal a fish-like appearance. After 24 hours, the muscle may become purple and hard due to congestion. When the fascia is cut, the muscle that still has vitality turns pink and herniates from the fascia incision. If the condition cannot be relieved, after blood flow is restored, edema may further worsen, and the muscle may present varying degrees of necrosis.

　　2. Under the microscope, some muscle fibers can maintain an intact appearance in the early stage of the lesion, while some muscle fibers exhibit nuclear loss and slight coagulation of the cytoplasm, showing granular changes, which are characteristic changes in the early stage of hypoxia. After 24 hours, some muscle fibers may swell and become glassy. In the late stage (48-72 hours), the damaged area shows the cross-striations and disappearance of the nuclei of muscle fibers. The specimens after amputation show that the regenerating muscle fibers appear mild to moderate变性, even necrosis.

　　3. Skeletal muscle accounts for about 42% of the body weight. Its complex structure contains a large number of biochemical substances, making this muscle tissue extremely sensitive to hypoxia. Under hypoxic conditions, these biochemical substances are released into the blood, and some of these substances are even harmful or fatal to the human body and are the main factors causing MMS. The cell membrane of muscle fiber cells plays an important role in the pathophysiological process of skeletal muscle. During ischemia, the concentration of adenosine triphosphate (ATP) in muscle cells significantly decreases, leading to abnormal changes in the permeability of the membrane, causing serious destruction of the intracellular and extracellular space configuration of the sarcoplasmic reticulum, resulting in abnormal transmembrane exchange of various biochemical substances, thus causing a series of metabolic syndromes. During the period of blood supply reconstruction and reperfusion, the affected limb produces a large number of oxygen free radicals, mainly including superoxide anions, hydrogen peroxide, and hydroxyl radicals. Oxygen free radicals are unstable in nature, highly reactive, and have cytotoxicity. Oxygen free radicals are very easy to react with thiol enzymes, proteins, lipids, and DNA, etc., destroying the chemical structure of tissue cells. Polyunsaturated fatty acids in the cell membrane are the most susceptible to oxygen free radicals, causing changes in the integrity of the biomembrane, further leading to the entry of biochemical substances in muscle cells into the blood, causing MMS and the necrosis of muscle cells.

　　4. Metabolic syndrome: Metabolic syndrome can be transient or persistent, and it is particularly evident after the reconstruction of blood supply.

　　(1) Metabolic acidosis: It almost occurs in all patients, but the degree varies. Metabolic acidosis originates from the accumulation of acidic metabolic products: tissue ischemia and hypoxia lead to a decrease in aerobic metabolism and an increase in anaerobic glycolysis, producing a large amount of lactic acid and pyruvic acid. Initially, the increase in the levels of both acids is consistent, but after that, the level of lactic acid rises faster than that of pyruvic acid, resulting in a decrease in blood pH and CO2 content, while the number of anions and cations significantly increases.

　　(2) Changes in electrolytes: Serum sodium ions are mostly within the normal range. Potassium ions are also within the normal range in the early stage. After the reconstruction of blood supply, muscle cells dissolve and release a large amount of potassium into the blood, resulting in a significant increase in blood potassium levels. Suddenly removing the vascular clip may lead to cardiac arrest. Hyperkalemia can cause arrhythmia and cardiac arrest. More than half of the patients are accompanied by hypocalcemia, hyperphosphatemia, and oliguria. The changes in the calcium-phosphorus ratio during the oliguria period are due to changes in the permeability of the muscle cell membrane. Under normal circumstances, the concentration of calcium ions in the extracellular fluid is 3 to 4 times higher than that in the intracellular fluid. If the muscle cell membrane is damaged, the concentration of calcium ions in the intracellular fluid increases until it is equal to that in the extracellular fluid, enhancing the contractility of muscle cells, causing stiffness in ischemic limbs and some MMS patients to experience muscle spasms during renal failure.

　　(3) Enzymatic changes: Before the restoration of blood supply, the plasma content of creatine phosphokinase (Creatine Phosphokinase, CPK) is slightly elevated, while the content in the venous blood of the affected limb is very high. After the restoration of blood supply, CPK is elevated again. The elevation of CPK, especially its isoenzyme CPK-MM, is a direct evidence of muscle damage, and a high level of CPK usually reflects progressive muscle necrosis. At this time, if the skin color is normal, it often leads to incorrect judgments, as intact skin does not reflect the normality of the underlying muscle tissue. In mild cases, CPK decreases a few hours or 1 to 2 days after the restoration of blood supply, while in more severe cases, CPK may rise to 1000 to 2000 U within a few days and return to normal 10 to 12 days later. In severe and fatal cases, CPK progressively increases, reaching over 20,000 U. All patients have elevated levels of lactate dehydrogenase (Lactate Dehydrogenase, LDH) and serum glutamic-oxaloacetic transaminase (Serum Glutamic-Oxaloacetic Transaminase, SGOT). The level of SGOT elevation is proportional to the degree of ischemia, and persistent elevation of SGOT indicates irreversible pathological damage to the muscle.

　　(4) Myoglobinuria: Within a few hours after vascular obstruction, urine output often decreases, and the urine appears cherry red due to the presence of myoglobin released from skeletal muscle breakdown. Myoglobinuria peaks at 48 hours and lasts for several days, with the degree of elevation related to the extent and severity of muscle breakdown. The myoglobin present in the urine is a granule that is positive for cresol, or aniline, or ortho-nitrophenol, and there are no red blood cells in the urine, while the plasma is clear. Myoglobinuria is often misdiagnosed as hemoglobinuria. Berman proposed the following differential methods: red plasma + red urine → hemoglobinuria; clear plasma + red urine → myoglobinuria. Specific qualitative testing methods for myoglobin include: chemical methods, spectrophotometric methods, and immunological methods. Markowiz reported a quantitative method for the determination of myoglobin in urine, making it possible to accurately detect myoglobin in blood and urine early.

　　(5) Myoglobinuria: The excretion of myoglobin by the kidneys may be delayed, with only small amounts excreted early, making it difficult to confirm the presence of myoglobinuria and leading to misdiagnosis. Therefore, when myoglobinuria is not detected, for patients highly suspected of having rhabdomyolysis, we should test for myoglobin in the blood.

　　(6) Acute renal failure: The degree of renal function impairment varies due to the extent of muscle ischemia, acidosis, and myoglobinuria. In mild to moderate cases, renal function is only temporarily and reversibly impaired, with a decrease in urine output, and most patients present with oliguria or anuria. Subsequently, the blood urea nitrogen and creatinine levels of the patients rise rapidly. In severe cases, severe acidosis with prolonged myoglobinuria occurs, and irreversible renal damage or even death will occur if dialysis is not performed immediately. Histological examination shows myoglobin casts in the renal tubules, containing a small amount of epithelial cells. The degree of acute tubular necrosis depends on the extent of myoglobin obstruction of the renal tubules, and this pathological change is often called myoglobinuric nephropathy. Sometimes this nephropathy synergizes with the glomerulosclerosis damage in the patient, severely affecting the prognosis. According to data from animal experiments and human autopsies, it is suggested that the mechanical obstruction of the renal tubules caused by myoglobin has a causal relationship with acute renal failure. However, whether myoglobin has direct toxicity to the renal tubules is still controversial, because experiments show that the injection of myoglobin does not cause acute renal failure.

　　Patients may experience restlessness, confusion, and disorientation, and in severe cases, complications such as ischemic spasm and acute renal failure may occur:

　　1. Ischemic spasm:Due to severe ischemia, the limb may cause muscle necrosis or contraction, and due to ischemic neuropathy and scar compression, nerve partial paralysis often occurs, resulting in severe disability of the limb.

　　2. Acute renal failure:The degree of renal function impairment varies due to the extent of muscle ischemia, acidosis, and myoglobinuria. In mild to moderate cases, renal function is only temporarily and reversibly impaired, with a decrease in urine output, and most patients present with oliguria or anuria. Subsequently, the blood urea nitrogen and creatinine levels of the patients rise rapidly. In severe cases, severe acidosis with prolonged myoglobinuria occurs, and irreversible renal damage or even death will occur if dialysis is not performed immediately.

　　1. Acute ischemic phase

　　The symptoms are severe pain in the affected limb, low skin temperature, pale complexion, cyanosis, abnormal or absent sensation, and the pain worsens with movement or examination of the limb. The most typical clinical manifestation of this stage is stiffness or rigidity after the limb becomes necrotic, especially in distal joints such as the knee and ankle, where a 'frozen' phenomenon occurs. The stiffness of the limb预示着代谢综合征的发生，after 12 to 24 hours, the limb becomes severely swollen, covering the entire affected limb. Sometimes the thigh is more prominent than the calf. The edema mainly occurs in the muscle tissue, and the swollen limb may present with softness, tightness, and a wooden texture, showing non-pitting. Due to the low skin temperature and cyanosis, it is often misdiagnosed as 'calf gangrene'. The main difference between the two is that this edema occurs in the muscle rather than subcutaneous tissue. Patients often experience restlessness, confusion, and disorientation. These neurological symptoms may be the result of the combined action of azotemia and other metabolic substances on the brain tissue. This stage is often accompanied by varying degrees of metabolic disturbances such as acidosis, azotemia, and hyperkalemia. If not corrected in time, it can cause serious complications and even death.

　　2. Reestablishment of blood supply and reperfusion period

　　During this period, clinical symptoms vary with the degree of ischemia. In severe cases, even though blood supply is restored, due to incomplete perfusion of distal tissues, pain does not subside but intensifies. Incomplete perfusion is due to the fact that the branches of intermuscular arteries are more severely blocked than the trunk, making blood supply difficult to restore. However, stiffness of muscles and joints is somewhat relieved, and the affected leg or forearm compartment syndrome still exists. After blood supply is restored, microthrombi of platelets and fibrin tissue can enter the pulmonary circulation, causing serious complications.

　　How to prevent myopathic nephrotic metabolic syndrome:

　　1. The number, range, and extent of occluded vessels.

　　2. Duration of occlusion.

　　3. The extent of involvement of intermuscular arteries and veins.

　　4. Early diagnosis of MMS.

　　5. Timely treatment measures for ischemia and early metabolic changes, including changes caused by free radicals. The incidence of gangrene leading to amputation is 30% to 50%; the mortality rate is 30% to 80%; the main cause of high mortality is hyperkalemia, difficult-to-control acidosis, and acute renal failure. Prevention: There is currently no relevant content description.

　　1. Blood test

　　The degree of elevation of blood potassium, CPK, SGOT, and LDH reflects the extent and range of skeletal muscle necrosis; an increase in blood myoglobin indicates the possibility of renal failure; a decrease in blood pH, especially after revascularization, further indicates poor prognosis.

　　2. Urine examination

　　The presence of myoglobin in urine should be a warning sign of renal failure.

　　3. Oxygen free radical detection

　　Due to its unstable chemical properties and short half-life, detection is somewhat difficult. It can be indirectly determined by measuring the malondialdehyde acid, which increases proportionally with the action of lipid peroxidation hydrogen peroxide, indicating the presence of oxygen free radicals.

　　1. Protein

　　The intake of protein should be determined according to the degree of renal function damage, but it should not exceed 1 gram per kilogram of body weight per day, and high-quality protein should reach more than 50%.

　　1. Recommended foods for high-quality protein: milk, crucian carp, egg white, dairy products, and fresh lean meat.

　　2. Foods to avoid: soy products and other plant proteins.

　　Second, High Vitamin and Folic Acid

　　Eat more foods rich in vitamin A, vitamin B2, folic acid, and vitamin C.

　　1. Recommended foods: tomatoes, green leafy vegetables, carrots, fresh jujube, watermelon, radish, cucumber, watermelon, citrus, orange, kiwi, and natural juices, etc.

　　2. Foods rich in vitamin B and folic acid: green leafy vegetables, etc.

　　3. For those with poor appetite, vitamin C preparations can be supplemented.

　　1. Immediate treatment before surgery involves supplementing lost fluids and correcting acid-base and electrolyte balance. Regardless of whether myoglobinuria is found, sodium bicarbonate should be administered to correct possible or existing acidosis and facilitate the excretion of myoglobin.

　　2. Perform thrombectomy or other necessary vascular reconstruction as soon as possible during and after surgery. Mannitol and alkaline drugs must be continuously administered during and after surgery to prevent further muscle damage until the blood pH value, especially the blood pH value of the affected limb, returns to normal. The use of alkaline drugs is particularly important when myoglobinuria is present, to prevent the deposition of myoglobin in the acidic environment of the renal tubules to form casts. At the same time, restore electrolyte balance, including reducing blood K to the normal range. If renal failure occurs, hemodialysis should be performed until renal function is restored.

　　3. Apply oxygen free radical scavengers to reduce further muscle damage caused by reperfusion of ischemic skeletal muscle. Augmentin (superoxide dismutase, SOD) and catalase (CAT) can respectively scavenging various sources of O2- and H2O2, and the combined application has a better effect. Peroxide Dismutase (POD) can convert H2O2 into water, thus avoiding the production of OH, which is more effective than Augmentin (SOD), catalase (CAT). Vitamin E can also be applied. Mannitol can both reduce cell edema and antioxidant free radicals, playing a protective role in myocardial and skeletal muscle.

　　4. Amputation should be performed if there is gangrene in the limbs. Even if there is no obvious necrosis, amputation should be performed to prevent the spread of metabolites from ischemic muscle tissue, especially when there is severe and widespread rhabdomyolysis.