High ALP levels can be caused by bone diseases, such as Paget's disease , osteomalacia , rickets , bone tumours, or tumours that have spread from another part of the body to the bone, or by overactive parathyroid glands hyperparathyroidism. Normal healing of a bone fracture can also raise ALP levels. Heart failure , heart attack, mononucleosis , or kidney cancer can raise ALP levels. A serious infection that has spread through the body sepsis can also raise ALP levels.
Low values Low levels of ALP can be caused by: Conditions that lead to malnutrition, such as celiac disease. A lack of nutrients in the diet. An inherited bone disease called hypophosphatasia. What Affects the Test Reasons you may not be able to have the test or why the results may not be helpful include: Taking medicines that may damage the liver, such as some antibiotics, birth control pills, long-term aspirin use, and oral diabetes medicines. Going through menopause.
Post-menopausal women may have higher ALP levels than women who still have menstrual cycles. Your age. Children normally have much higher ALP levels than adults because rapid bone growth is normal in children and bones make ALP. Drinking a lot of alcohol. If liver disease is suspected, more blood tests, an ultrasound , or a CT scan are generally recommended to find the problem. Other tests to check liver function, such as alanine aminotransferase, aspartate aminotransferase, and bilirubin, may be done at the same time as an alkaline phosphatase ALP test.
Manual of Laboratory and Diagnostic Tests , 8th ed. Philadelphia: Lippincott Williams and Wilkins. Laboratory Tests and Diagnostic Procedures, 5th ed. Louis: Saunders. Manual of Laboratory and Diagnostic Tests, 8th ed.
Mosby's Manual of Diagnostic and Laboratory Tests, 4th ed. B Disease states in which increase, decrease, or dysregulation of hAPs is either indicative or causative.
The most direct link between APs and human disease is hypophosphatasia HPP , a disease characterized by mutations in TNAP associated with decreased enzyme activity in specific organs 10 , 11 Figure 1 B. This decrease in AP activity results in variable symptoms that range from perinatal HPP that can result in still birth from profound skeletal hypomineralization 11 , 12 , potentially lethal seizures in infantile HPP 13 — 15 , to milder phenotypes such as bone fractures and periodontal disease in juvenile HPP and adult HPP 16 , Tissue non-specific AP is anchored to the cell membranes of osteoblasts and chondrocytes and to matrix vesicles released by those cells, where it degrades PPi to Pi.
PPi is an inhibitor of mineralization 18 and regulation by TNAP controls propagation of extracellular mineralization of apatite crystals. TNAP deficiency increases the amount of inhibitory PPi thus decreasing extracellular mineralization, and humans with HPP show a loss of mineralization fronts Pyridoxalphosphate, the active form of vitamin B6 24 , is elevated in the serum of HPP patients 25 , PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures 29 , TNAP is expressed during embryonic neural and spinal chord development, and promotes axonal growth in vitro and neurogenesis in adults 31 , suggesting an importance in proper neural function.
TNAP upregulation in the vasculature contributes to medial vascular calcification causing vascular stiffening and eventually heart failure 34 , An emerging function for TNAP is regulation of purinergic signaling. Extracellular ATP and ADP, through the binding of nucleotide receptors, act as signals inducing inflammation after an acute event such as necrosis induced by damage or infection that releases intracellular nucleotides.
In contrast, degradation of extracellular ATP and ADP to AMP and adenine causes cessation of inflammatory signaling, and induction through adenine receptors of an anti-inflammation response 36 , Intestinal AP is expressed in villus-associated enterocytes where it regulates fatty acid absorption through secretion of vesicles at both the luminal and basolateral surfaces 41 , 42 , regulates bicarbonate secretion and duodenal surface pH 43 , and has been implicated in the regulation of diet-induced obesity 44 , 45 and metabolic syndrome 46 , 47 Figure 1 A.
But perhaps, the most remarkable function of IAP centers on its protective interactions with the bacterial symbionts that inhabit or invade our enteric system. IAP has been shown to dephosphorylate detoxify the lipid A moiety of lipopolysaccharide LPS , the outer lipid layer of the outer membrane of Gram-negative bacteria Intestinal AP deficiency has been associated with inflammation in the human intestine 53 and in the intestines of vertebrate models in which AP levels are decreased Supplementation of IAP to animals where intestinal inflammation is induced directly or indirectly with antibiotic use for example reduces inflammation 53 , 55 , In addition, a protective role has been ascribed to IAP in mouse models of necrotizing enterocolitis 57 — This protective role may include IAP-dependent shaping 60 and homeostasis 61 of the microbiome.
Along with direct regulation of intestinal homeostasis, IAPs and LPS detoxification have been implicated in other immune-related processes including prevention of bacterial translocation by endogenous or pharmacologically administered IAPs 62 — 64 , and resolution of intestinal inflammation and tissue regeneration 65 — It should also be noted that in addition to vertebrate IAP, TNAP has been shown to dephosphorylate LPS when it is applied to tissue sections from rat livers 68 and in the mouse uterus With the current and increasing interest in the microbiome, IAP function as it relates to interaction with the endogenous microbes and its influence on human health will undoubtedly be clarified in the coming years.
Although there are a multitude of AP studies focusing on vertebrate models of disease, there are relatively few publications to date reporting pharmacological use of APs as a treatment in humans. However, there were at least 11 clinical trials concerning AP treatment of HPP, 3 concerning AP treatment of sepsis with renal injury or failure, 2 concerning AP treatment during or after cardiac surgery, and at least 1 each concerning AP treatment of rheumatoid arthritis, and ulcerative colitis UC.
AP enzyme replacement therapy is also currently available to treat HPP. A recombinant soluble human TNAP has been approved for use in perinatal, infantile, and juvenile-onset HPP 70 , 71 and has proven successful in symptom improvement and survival in perinatal and infantile HPP 72 , In addition to HPP, use of AP as treatment increased renal function in sepsis-induced acute kidney injury 74 , 75 and showed short-term improvement of severity of UC in patients with moderate-to-severe UC These studies are a first glimpse into AP use as a treatment for disease, with very positive results.
Given the jack of all trades nature of APs and the potential for APs as pharmacological agents in various diseases, studies like these should increase in the coming years.
The ability of APs to detoxify LPS appears to be an evolutionarily conserved function as it was recently implicated in symbiont recognition and homeostasis in the invertebrate squid- Vibrio symbiosis model As it is becoming clear that metazoans developed in a microbial world 78 , it seems likely that APs have been and may continue to be an evolutionary force shaping the diversity and function of our endogenous microbial populations.
Indeed, alterations in IAP have been shown to influence the composition of the intestinal microbiome We can even expand this thinking—if hAPs evolved from an ancient ancestral bacterial AP, then APs may have had a prominent role in shaping basic human biochemistry in addition to our interactions with microbes, and thus exerted a profound influence on human health. The reader of this review will notice that many of the articles cited might be considered old, with contributions from the s, s, and s.
In fact, the study of APs goes back close to years when a bone enzyme freeing phosphate was first mentioned by Robison and Soames The recent resurgence of interest in APs, should it continue, will hopefully provide more insight into all aspects of AP biology, especially as it relates to health. The ubiquity and functions of AP distinguish them as unconventional immune proteins, and to this writer, APs are unendingly fascinating.
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases.
Protein Sci — Weinheim: Wiley-VCH Google Scholar. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev — Intestinal alkaline phosphatase: novel functions and protective effects. Microdiversity of extracellular enzyme genes among sequenced prokaryotic genomes. ISME J — Dynamic evolution of the LPS-detoxifying enzyme intestinal alkaline phosphatase in zebrafish and other vertebrates.
Front Immunol Multisystemic functions of alkaline phosphatases. ALP is made mostly in the liver and in bone with some made in the intestines and kidneys. It also is made by the placenta of a pregnant woman. The liver makes more ALP than the other organs or the bones.
Some conditions cause large amounts of ALP in the blood. These conditions include rapid bone growth during puberty , bone disease such as Paget's disease or cancer that has spread to the bones , a disease that affects how much calcium is in the blood hyperparathyroidism , vitamin D deficiency, or damaged liver cells.
If the ALP level is high, more tests may be done to find the cause. The amounts of different types of ALP in the blood may be measured and used to determine whether a high level is from the liver or bones. This is called an alkaline phosphatase isoenzymes test. A health professional uses a needle to take a blood sample, usually from the arm. When a blood sample is taken, you may feel nothing at all from the needle. Or you might feel a quick sting or pinch.
There is very little chance of having a problem from this test. When a blood sample is taken, a small bruise may form at the site.
Each lab has a different range for what's normal. Metrics details. Alkaline phosphatase ALP is an important enzyme mainly derived from the liver, bones and in lesser amounts from intestines, placenta, kidneys and leukocytes. An increase in ALP levels in the serum is frequently associated with a variety of diseases.
This study was done in order to determine the diseases associated with a high ALP level among Thai adult hospitalized patients. Excluded were cases of a patients who have bone involvements with malignancies, b pediatric patients younger than 15 years old and c HIV-seropositive patients.
A total of hospitalized patients with eligible medical records were identified 96 males and 85 females, mean age High serum ALP levels in hospitalized patients were commonly found in three major groups having obstructive biliary diseases, infiltrative liver disease and sepsis.
The study results were in accordance with previous reports in developed countries. Nonetheless, cholangiocarcionoma and some tropical diseases unique to our setting were also detected in these cases.
Peer Review reports. In healthy adults, this enzyme is mainly derived from the liver, bones and in lesser amounts from intestines, placenta, kidneys and leukocytes. An increase in serum ALP levels is frequently associated with a variety of diseases. Such disorders as extrahepatic bile obstruction, intrahepatic cholestasis, infiltrative liver disease and hepatitis are mentioned. Unfortunately, the elevation of ALP less than three times the normal level is considered non specific and insufficient to provide a definite diagnosis.
Markedly elevated serum ALP, hyperalkalinephosphatasemia, is seen predominantly with more specific disorders, including, malignant biliary obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, hepatic lymphoma and sarcoidosis.
This study was performed as a retrospective study. This study focused on a one-year period, from January to December Exclusion was made in cases of a patients who have bone involvements with malignancies, b pediatric patients younger than 15 years old and c HIV seropostive patients. The review of the patients' medical records during this period identified cases with a conclusive diagnosis for further analysis. The data from the discharge summary of these patients were then recorded including their age and sex, as well as the final diagnosis.
Descriptive statistics were used in analyzing the patient characteristics and laboratory parameters for each group. In addition, unpaired Student's T test was used to assess group differences when appropriate. Independence was tested by Chi square test.
All the statistical analyses in this study were made using SPSS 7. They were male and 96 female patients with ages ranging from 21 to 90 years old mean age The most common diagnosis in patients with high ALP in our series was malignant biliary obstruction.
0コメント