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What causes high serum alkaline phosphatase (ALP)?
1. Hepatobiliary diseases

When there are hepatobiliary diseases (such as hepatocellular injury, bile duct obstruction; hepatocellular and bile duct epithelial cell hyperplasia or carcinoma), the total activity of serum ALP can be elevated. In hepatobiliary diseases accompanied by jaundice, simultaneous determination of ALT and AST vitality helps to differentiate hepatocellular jaundice from cholestatic jaundice. In patients with hepatocellular jaundice, ALP activity is elevated, but the increase is small, not exceeding 3-5 times the upper reference limit, and ALP and total bilirubin do not change in parallel. In contrast, ALP activity is elevated early and to a large extent in patients with obstructive jaundice. The enzyme activity of complete obstructive jaundice is higher than that of intrahepatic obstruction; those with tumor-induced obstruction are higher than those with stone-induced obstruction, and the degree of elevation is in line with the change of total bilirubin. 73%-95% of patients with intrahepatic space-occupying lesions, such as primary or secondary hepatocellular carcinoma, have significantly elevated ALP. Hepatobiliary diseases without jaundice, such as hepatitis without jaundice, chronic hepatitis, and fatty liver, have mildly elevated serum ALP, and localized lesions, such as liver abscesses, should be considered if they are markedly elevated and accompanied by elevated ALT. ALP vigor varies in cirrhosis and is not associated with changes in total bilirubin. If the serum bilirubin increases gradually, but ALP decreases, it is a sign of deterioration; on the contrary, it indicates regeneration of hepatocytes. The use of chlorpromazine, arsine, methyltestosterone, and oral contraceptives can cause cholestasis, which elevates serum ALP before bilirubin. The increase in serum ALP in hepatobiliary disease may be due to increased release of ALP from cell membranes dissolved by accumulated bile acids, or impaired excretion of bile from hepatocytes to the intestinal lumen via capillary bile ducts or bile ducts, or increased synthesis of ALP by hepatocytes induced by factors that impede bile excretion. Histochemistry confirmed that ALP activity was decreased in hepatocellular carcinoma tissues and significantly increased in compressed liver tissues surrounding the carcinoma. It is suggested that liver occupying lesions with increased serum ALP viability are due to compressive infarction of the bile ducts in the liver tissue around the lesion, resulting in impaired excretion of ALP and hyperproduction of ALP by hepatocytes around the lesion.

2, skeletal disorders

Skeletal disease patients mainly due to the proliferation of osteoblasts so that serum ALP is elevated. Deformational osteitis (Paget's disease) is significantly elevated, for the upper limit of the normal reference value of 10 times to dozens of times, but the serum calcium and phosphorus is more normal. ALP changes in patients with rickets and osteomalacia are related to the course of the disease and the condition, with mild elevation of ALP in the early stage and a persistent rise with aggravation of the disease, up to 4-10 times the upper limit of normal. Enzyme activity decreases after 2 weeks of treatment. ALP activity is mildly elevated in fracture healing and significantly elevated in osteogenic bone cancer. ALP does not change significantly in various types of osteoporosis, benign osteoblastoma, etc. ALP activity is moderately or severely elevated in patients with hyperparathyroidism due to enhanced osteolysis caused by excess parathyroid hormone, along with elevated blood calcium and decreased blood phosphorus. This is useful in differentiating from deformational osteitis and rickets, where ALP3 is derived primarily from actively growing bone and is often difficult to separate from ALP2 on electrophoresis. It is increased in malignant osteitis or osteosarcoma, secondary or osseous bone cancer, rickets, or hyperthyroidism.

Serum ALP is higher than normal in 40%-80% of patients with osteosarcoma and is associated with the prognosis of patients with osteosarcoma. The prognosis of osteosarcoma patients is poorer if they have high serum ALP prior to amputation. Pre-treatment serum ALP activity was associated with prognosis. The time from initiation of treatment to recurrence was 21.2 months in the normal blood ALP group and 13.9 months in the elevated ALP group. It is believed that patients with high pre-treatment blood ALP values may be treated with a more lethal chemotherapy regimen to improve survival.

3, malignant tumors

Determination of the serum ALP composition of 4000 people showed that its main role is to identify whether the elevated ALP in serum is individually or simultaneously from liver and bone tissue. The presence of both hepatic and bone-type ALP elevations in the blood is most commonly associated with malignant tumors. Increased hepatic ALP is almost always the result of infiltration by a hepatic malignancy. Secondary deposition of hepatic-type ALP in bone tissue often causes an osteogenic response and is thus accompanied by increased bone-type ALP. Therefore, the proportion of patients with malignant tumors with both liver-type and bone-type serum increased is large, and the quantitative determination of liver-type and bone-type ALP isoenzymes is of great value in judging both the spread of the tumor and the efficacy of the treatment. Early placental-type ALP was found in the serum and cancer tissues of lung cancer patients without bone metastasis, and this enzyme was also found in the serum of patients with meningioma, pancreatic cancer, and craniopharyngioma. Regan isoform (or oncogenic isoform) is produced when the normally repressed gene corresponding to ALP is re-expressed and is found in tumors of the lung, colon, breast, and female reproductive system.Nagao isoform (embryonic-like ALP), which is similar in nature to ALP4, is found in serum from patients with pancreatic, pleural, and biliary tract cancers. Using specific monoclonal antibody to regularly test the serum HMAP content of ovarian cancer patients after surgery, it is found that it can better reflect the patient's condition and tumor activity, and it is believed that HMAP is similar to CEA, which can be found in a variety of malignant tumors and based on certain hematological diseases, such as lymphoma, leukemia, and so on.

4. During pregnancy, ALP4 in serum shows a regular increase, especially in the last 3 months with an exponential increase. It often shows a sudden decrease before delivery, and 3-4d postpartum, 50% of serum ALP4 disappears, which is more obvious in menstruating mothers than primigravid women. Serum ALP4 was significantly increased in patients with preeclampsia before the onset of overt clinical symptoms, and significantly decreased in pregnant women with high-risk pregnancies due to hypertension and diabetes mellitus. A significant increase is indicative of placental damage and a decrease is characteristic of placental dysplasia. Therefore, serum ALP4 is an indication to monitor the functional status of the placenta.

5, other diseases

Uremia, intestinal obstruction, ALP2 increased. In renal damage, there is a significant increase in urinary ALP viability due to the release of this enzyme from renal cell destruction. Renal ALP was detected in serum after rejection of renal transplantation.ALP6 was found in serum of patients with active ulcerative colitis, while ALP2 disappeared; after improvement in treatment, ALP6 disappeared and ALP2 reproduced. This proves that ALP2 is closely related to ALP6, and ALP6 may be a modifying enzyme of ALP2. ALP activity can be seen after intestinal-like deformation of the gastric mucosa in patients with chronic gastritis, and increases with the expansion of the deformation range