関: familial hypophosphatemia、phosphaturia

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/27 23:05:48」(JST)

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Hypophosphatemia is an electrolyte disturbance in which there is an abnormally low level of phosphate in the blood. The condition has many causes, but is most commonly seen when malnourished patients (especially chronic alcoholics) are given large amounts of carbohydrates, which creates a high phosphorus demand by cells, removing phosphate from the blood (refeeding syndrome).

Because a decrease in phosphate in the blood is sometimes associated with an increase in phosphate in the urine, the terms hypophosphatemia and "phosphaturia" are occasionally used interchangeably; however, this is improper since there exist many causes of hypophosphatemia besides overexcretion and phosphaturia, and in fact the most common causes of hypophosphatemia are not associated with phosphaturia.

Common causes of hypophosphatemia

Refeeding syndrome This causes a demand for phosphate in cells due to the action of Hexokinase, an enzyme that attaches phosphate to glucose to begin metabolism of glucose. Also, production of ATP when cells are fed and recharge their energy supplies, requires phosphate.
Respiratory alkalosis Any alkalemic condition moves phosphate out of the blood into cells. This includes most common respiratory alkalemia (a higher than normal blood pH from low carbon dioxide levels in the blood), which in turn is caused by any hyperventilation (such as may result from sepsis, fever, pain, anxiety, drug withdrawal, and many other causes). This phenomenon is seen because in respiratory alkalosis carbon dioxide (CO2) decreases in the extracellular space, causing intracellular CO2 to freely diffuse out of the cell. This drop in intracellular CO2 causes a rise in cellular pH which has a stimulating effect on glycolysis. Since the process of glycolysis requires phosphate (the end product is adenosine triphosphate), the result is a massive uptake of phosphate into metabolically active tissue (such as muscle) from the serum. It is interesting to note, however, that this effect is not seen in metabolic alkalosis, for in such cases the cause of the alkalosis is increased bicarbonate rather than decreased CO2. Bicarbonate, unlike CO2, has poor diffusion across the cellular membrane and therefore there is little change in intracellular pH. ^[1]
Alcohol abuse Alcohol impairs phosphate absorption. Alcoholics are usually also malnourished with regard to minerals. In addition, alcohol treatment is associated with refeeding, and the stress of alcohol withdrawal may create respiratory alkalosis, which exacerbates hypophosphatemia (see above).
Malabsorption This includes GI damage, and also failure to absorb phosphate due to lack of vitamin D, or chronic use of phosphate binders such as sucralfate, aluminum-containing antacids, and (more rarely) calcium-containing antacids.

Primary hypophosphatemia is the most common cause of nonnutritional rickets. Laboratory findings include low-normal serum calcium, moderately low serum phosphate, elevated serum alkaline phosphatase, and low serum 1,25 dihydroxy-vitamin D levels, hyperphosphaturia, and no evidence of hyperparathyroidism.^[2]

Other rarer causes include

Certain blood cancers such as lymphoma or leukemia
Hereditary causes
Liver failure
Tumor-induced osteomalacia

Pathophysiology

Hypophosphatemia is caused by the following three mechanisms:

Inadequate intake (often unmasked in refeeding after long-term low phosphate intake)
Increased excretion (e.g. in hyperparathyroidism, hypophosphatemic rickets)
Shift from extracellular to intracellular space (seen in treatment of diabetic ketoacidosis, refeeding, short-term increases in cellular demand (e.g., hungry bones syndrome) and acute respiratory alkalosis)

Major signs and symptoms

Muscle dysfunction and weakness. This occurs in major muscles, but also may manifest as: diplopia, low cardiac output, dysphagia, and respiratory depression due to respiratory muscle weakness.
Mental status changes. This may range from irritability to gross confusion, delirium, and coma.
White cell dysfunction, causing worsening of infections.
Instability of cell membranes due to low ATP levels: this may cause rhabdomyolysis with increased CPK, and also hemolytic anemia.
Increased affinity for oxygen in the blood caused by decreased production of 2,3BPG.
Large pulp chambers in the teeth.

Treatment

Standard intravenous preparations of potassium phosphate are available and are routinely used in malnourished patients and alcoholics. Oral supplementation also is useful where no intravenous treatment is available. Historically one of the first demonstrations of this was in concentration camp victims who died soon after being re-fed: it was observed that those given milk (high in phosphate) had a higher survival rate than those who did not get milk.^{[citation needed]}

Monitoring parameters during correction with IV phosphate^[3]

Phosphorus levels should be monitored after 2 to 4 hours after each dose, also monitor serum potassium, calcium and magnesium. Cardiac monitoring is also advised.

External links

eMedicine review
Tutorial - complications
Refeeding Syndrome

References

^ O'Brien, Thomas M; Coberly, LeAnn (2003). "Severe Hypophosphatemia in Respiratory Alkalosis" (PDF). Advanced Studies in Medicine 3 (6): 347.
^ Toy, Girardet, Hormann, Lahoti, McNeese, Sanders, and Yetman. Case Files: Pediatrics, Second Edition. 2007. McGraw Hill.
^ Shajahan, A., Ajith Kumar, J., Gireesh Kumar, K. P., Sreekrishnan, T. P. and Jismy, K. (2015), Managing hypophosphatemia in critically ill patients: a report on an under-diagnosed electrolyte anomaly. Journal of Clinical Pharmacy and Therapeutics. doi: 10.1111/jcpt.12264

UpToDate Contents

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1. 低リン血症の原因 causes of hypophosphatemia
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English Journal

Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis.

Tagliabracci VS1, Engel JL, Wiley SE, Xiao J, Gonzalez DJ, Nidumanda Appaiah H, Koller A, Nizet V, White KE, Dixon JE.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2014 Apr 15;111(15):5520-5. doi: 10.1073/pnas.1402218111. Epub 2014 Mar 26.
The family with sequence similarity 20, member C (Fam20C) has recently been identified as the Golgi casein kinase. Fam20C phosphorylates secreted proteins on Ser-x-Glu/pSer motifs and loss-of-function mutations in the kinase cause Raine syndrome, an often-fatal osteosclerotic bone dysplasia. Fam20C
PMID 24706917

Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis.

Nomura K1, Tatsumi S, Miyagawa A, Shiozaki Y, Sasaki S, Kaneko I, Ito M, Kido S, Segawa H, Sano M, Fukuwatari T, Shibata K, Miyamoto K.
Journal of the American Society of Nephrology : JASN.J Am Soc Nephrol.2014 Apr;25(4):761-72. doi: 10.1681/ASN.2013060569. Epub 2013 Nov 21.
Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal
PMID 24262791

Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia.

Carpenter TO, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Wooddell MM, Kawakami T, Ito T, Zhang X, Humphrey J, Insogna KL, Peacock M.
The Journal of clinical investigation.J Clin Invest.2014 Apr 1;124(4):1587-97. doi: 10.1172/JCI72829. Epub 2014 Feb 24.
BACKGROUND: X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate reabsorption, and low serum concentrations of phosphate (inorgani
PMID 24569459

Japanese Journal

A case of zoledronate-induced tubulointerstitial nephritis with Fanconi syndrome

, , , ,
Endocrine Journal 59(12), 1051-1056, 2012
… Moreover, development of glucosuria, hypophosphatemia, hyperphosphaturia, hyponatremia, hypouricemia, and high β2-microglobulin/NAG, together with histopathological findings compatible with renal tubular injury/interstitial nephritis on renal biopsy, allowed the diagnosis of Fanconi syndrome. …
NAID 130004443777

Effects of Chronic NH_4Cl Dosage and Swimming Exercise on Bone Metabolic Turnover in Rats

,
Journal of physiological anthropology and applied human science 24(6), 595-600, 2005-11
… These results suggest that blood Ca and P concentrations in the chronic acidosis condition during the 4-weeks might be maintained by hypercalciuria and hyperphosphaturia with kidney disorder, and swimming exercise training leads to decrease in BMD with stimulation of bone resorption and reduction of body fat. …
NAID 110002555257

Fanconi症候群を合併したSjögren症候群の1例

浦上正弘,藤本隆,嶋宏子,金内雅夫,花谷正和,土肥和紘
奈良医学雑誌 45(1), 44-50, 1994-02-28
… In view of glucosuria without hyperglycemia, hypophosphatemia, hyperphosphaturia, and aminoaciduria, the diagnosis of Fanconi's syndrome was made. …
NAID 120004973628

Related Pictures

★リンクテーブル★

リンク元	「phosphaturia」「高リン酸尿症」「familial hypophosphatemia」

「phosphaturia」

Hypophosphatemia
	Phosphate group chemical structure
Classification and external resources
Specialty	endocrinology
ICD-10	E83.3
ICD-9-CM	275.3
DiseasesDB	6503
MedlinePlus	000307
eMedicine	med/1135
Patient UK	Hypophosphatemia
MeSH	D017674
	[edit on Wikidata]