Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary defects in the renal handling of filtered NaCl and water have important implications for understanding the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Null mutations in the water channel aquaporin 1 (AQP1) or the Na/H exchanger NHE3, two major fluid transporters in the proximal tubule, are states in which a reduction in proximal fluid absorption is accompanied by proportionate decrements in glomerular filtration rate. Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either AQPI or NHE3 deficiency. On the other hand, severe syndromes of salt wasting are caused by transport deficiencies in the thick ascending limb or the collecting duct, indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. Loss of function of the Na,K,2Cl-cotransporter (NKCC2) or of the epithelial Na channel (ENaC) reduces Na absorption in thick ascending limbs or collecting ducts. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load, intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is remarkably insufficient, particularly in the immature kidney of the newborn.
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PMID:NaCl transport deficiencies--hemodynamics to the rescue. 1078 41

Animals with induced or natural null mutations in renal NaCl and water transporter genes provide a powerful tool to study the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Deficiencies in the Na/H exchanger NHE3 and in the water channel aquaporin 1 (AQP1) cause reductions in proximal fluid absorption which are accompanied by proportionate decrements in glomerular filtration rate (GFR). Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either NHE3 or AQP1 deficient animals. On the other hand, severe syndromes of salt wasting are caused by loss of function of the Na,K,2Cl-cotransporter (NKCC2) in the thick ascending limb, or of the epithelial Na channel (ENaC) the collecting duct indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is sometimes insufficient, particularly in the immature kidney of the newborn.
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PMID:Sodium transport deficiency and sodium balance in gene-targeted mice. 1167 27

Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyperreninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na-K-2Cl-cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor-mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed.
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PMID:The role of cyclooxygenases and prostanoid receptorsin furosemide-like salt losing tubulopathy: the hyperprostaglandin E syndrome. 1528 66