-
Pflugers Archiv : European Journal of... Apr 2024Secretin is a key hormone of the intestinal phase of digestion which activates pancreatic, bile duct and Brunner gland HCO secretion. Recently, the secretin receptor... (Review)
Review
Secretin is a key hormone of the intestinal phase of digestion which activates pancreatic, bile duct and Brunner gland HCO secretion. Recently, the secretin receptor (SCTR) was also found in the basolateral membrane of the beta-intercalated cell (B-IC) of the collecting duct. Experimental addition of secretin triggers a pronounced activation of urinary HCO excretion, which is fully dependent on key functional proteins of the B-IC, namely apical pendrin and CFTR and the basolateral SCTR. Recent studies demonstrated that the SCTR knock-out mouse is unable to respond to an acute base load. Here, SCTR KO mice could not rapidly increase urine base excretion, developed prolonged metabolic alkalosis and exhibited marked compensatory hypoventilation. Here, we review the physiological effects of secretin with distinct focus on how secretin activates renal HCO excretion. We describe its new function as a hormone for HCO homeostasis.
Topics: Mice; Animals; Secretin; Cell Membrane; Sulfate Transporters; Biological Transport; Homeostasis; Bicarbonates
PubMed: 38221598
DOI: 10.1007/s00424-024-02906-3 -
American Journal of Translational... 2022Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy caused by biallelic inactivating mutations in the SLC12A3 gene. This gene encodes the... (Review)
Review
Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy caused by biallelic inactivating mutations in the SLC12A3 gene. This gene encodes the thiazide-sensitive sodium-chloride cotransporter (NCC) which is exclusively expressed in the distal convoluted tubules (DCT). GS patients classically present with hypokalemic metabolic alkalosis with hypocalciuria and hypomagnesemia. While hypokalemia and metabolic alkalosis are easily explained by effects of the genotypic defect in GS, the mechanisms by which hypomagnesemia and hypocalciuria develop in GS are poorly understood. In this review, we aim to achieve three major objectives. First, present a concise discussion about current understanding on physiologic calcium and magnesium handling in the DCT. Second, integrate expression data from studies on calciotropic and magnesiotropic proteins relevant to the GS disease state. Lastly, provide insights into the possible mechanisms of calcium-magnesium crosstalk relating to the co-occurrence of hypocalciuria and hypomagnesemia in GS models. Our analyses highlight specific areas of study that are valuable in elucidating possible molecular pathways of hypocalciuria and hypomagnesemia in GS.
PubMed: 35173827
DOI: No ID Found -
Current Opinion in Nephrology and... Jan 2021Pendrin resides on the luminal membrane of type B intercalated cells in the renal collecting tubule system mediating the absorption of chloride in exchange for... (Review)
Review
PURPOSE OF REVIEW
Pendrin resides on the luminal membrane of type B intercalated cells in the renal collecting tubule system mediating the absorption of chloride in exchange for bicarbonate. In mice or humans lacking pendrin, blood pressure is lower, and pendrin knockout mice are resistant to aldosterone-induced hypertension. Here we discuss recent findings on the regulation of pendrin.
RECENT FINDINGS
Pendrin activity is stimulated during alkalosis partly mediated by secretin. Also, angiotensin II and aldosterone stimulate pendrin activity requiring the mineralocorticoid receptor in intercalated cells. Angiotensin II induces dephosphorylation of the mineralocorticoid receptor rendering the receptor susceptible for aldosterone binding. In the absence of the mineralocorticoid receptor in intercalated cells, angiotensin II does not stimulate pendrin. The effect of aldosterone on pendrin expression is in part mediated by the development of hypokalemic alkalosis and blunted by K-supplements or amiloride. Part of the blood pressure-increasing effect of pendrin is also mediated by its stimulatory effect on the epithelial Na-channel in neighbouring principal cells.
SUMMARY
These findings identify pendrin as a critical regulator of renal salt handling and blood pressure along with acid--base balance. A regulatory network of hormones fine-tuning activity is emerging. Drugs blocking pendrin are being developed.
Topics: Aldosterone; Angiotensin II; Animals; Bicarbonates; Blood Pressure; Chlorides; Humans; Kidney; Kidney Tubules, Collecting; Mice; Phosphorylation; Receptors, Mineralocorticoid; Sulfate Transporters
PubMed: 33186222
DOI: 10.1097/MNH.0000000000000669 -
Clinical Practice and Cases in... May 2024Diabetic ketoacidosis (DKA) is a common diagnosis in the emergency department (ED). However, one must consider other causes for acid-base disturbances when the pattern...
INTRODUCTION
Diabetic ketoacidosis (DKA) is a common diagnosis in the emergency department (ED). However, one must consider other causes for acid-base disturbances when the pattern is not consistent with typical presentation.
CASE REPORT
A 52-year-old female with a history of insulin-dependent diabetes mellitus type 2 presented to the ED with abdominal pain, nausea, and vomiting for three days. Her diagnostic workup revealed diabetic ketoacidosis but with concurrent metabolic alkalosis. Standard treatment for DKA was initiated, and there was improvement of her mentation and resolution of metabolic derangements.
CONCLUSION
Overlooking a diagnosis of DKA because of alkalosis on venous blood gas testing could lead to inappropriate treatment and, therefore, increased risk of morbidity and mortality in the affected patient.
PubMed: 38869331
DOI: 10.5811/cpcem.1389 -
Paediatric Anaesthesia Jul 2020Infantile hypertrophic pyloric stenosis (IHPS) leads to excessive vomiting and metabolic alkalosis, which may subsequently cause apnea. Although it is generally assumed... (Review)
Review
BACKGROUND
Infantile hypertrophic pyloric stenosis (IHPS) leads to excessive vomiting and metabolic alkalosis, which may subsequently cause apnea. Although it is generally assumed that metabolic derangements should be corrected prior to surgery to prevent apnea, the exact incidence of perioperative apneas in infants with IHPS and the association with metabolic alkalosis are unknown. We performed this systematic review to assess the incidence of apnea in infants with IHPS and to verify the possible association between apnea and metabolic alkalosis.
METHODS
We searched MEDLINE, Embase, and Cochrane library to identify studies regarding infants with metabolic alkalosis, respiratory problems, and hypertrophic pyloric stenosis. We conducted a descriptive synthesis of the findings of the included studies.
RESULTS
Thirteen studies were included for analysis. Six studies described preoperative apnea, three studies described postoperative apnea, and four studies described both. All studies were of low quality or had other research questions. We found an incidence of 27% of preoperative and 0.2%-16% of postoperative apnea, respectively. None of the studies examined the association between apnea and metabolic alkalosis in infants with IHPS.
CONCLUSIONS
Infants with IHPS may have a risk to develop perioperative apnea. However, the incidence rates should be interpreted with caution because of the low quality and quantity of the studies. Therefore, further studies are required to determine the incidence of perioperative apnea in infants with IHPS. The precise underlying mechanism of apnea in these infants is still unknown, and the role of metabolic alkalosis should be further evaluated.
Topics: Apnea; Humans; Incidence; Infant; Pyloric Stenosis, Hypertrophic
PubMed: 32298502
DOI: 10.1111/pan.13879 -
Frontiers in Physiology 2022In 2009, two groups independently linked human mutations in the inwardly rectifying K channel Kir4.1 (gene name ) to a syndrome affecting the central nervous system... (Review)
Review
In 2009, two groups independently linked human mutations in the inwardly rectifying K channel Kir4.1 (gene name ) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na, K, and Mg with urine, activation of the renin-angiotensin-aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies.
PubMed: 35370765
DOI: 10.3389/fphys.2022.852674 -
Pediatric Nephrology (Berlin, Germany) Oct 2020Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at... (Review)
Review
Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.
Topics: Bartter Syndrome; Chloride Channels; Gitelman Syndrome; Humans; Kidney Tubules, Distal; Loop of Henle; Mutation; Renal Reabsorption; Sodium
PubMed: 31664557
DOI: 10.1007/s00467-019-04371-y -
Cureus Apr 2023Milk-alkali syndrome is described by a triad of elevated levels of calcium, metabolic alkalosis, and acute kidney injury that historically occurred as a result of the...
Milk-alkali syndrome is described by a triad of elevated levels of calcium, metabolic alkalosis, and acute kidney injury that historically occurred as a result of the combined intake of large amounts of calcium and absorbable alkali. It is becoming common recently with the use of over-the-counter calcium supplements for osteoporosis treatment in postmenopausal women. We present a case of a 62-year-old female who presented with generalized weakness. She was noted to have severe hypercalcemia, and impaired renal function with a significant history of daily over-the-counter calcium supplement use and as-needed calcium carbonate use for gastroesophageal reflux disease (GERD). This case highlights the stepwise approach to the evaluation and management of hypercalcemia. She was appropriately treated with the resolution of hypercalcemia and presenting symptoms.
PubMed: 37252584
DOI: 10.7759/cureus.38171 -
Journal of Nephrology Mar 2023Renal tubules play an important role in maintaining water, electrolyte, and acid-base balance. Renal tubule dysfunction can cause electrolyte disorders and acid-base... (Review)
Review
Renal tubules play an important role in maintaining water, electrolyte, and acid-base balance. Renal tubule dysfunction can cause electrolyte disorders and acid-base imbalance. Clinically, hypokalemic renal tubular disease is the most common tubule disorder. With the development of molecular genetics and gene sequencing technology, hereditary renal tubular diseases have attracted attention, and an increasing number of pathogenic genes related to renal tubular diseases have been discovered and reported. Inherited renal tubular diseases mainly occur due to mutations in genes encoding various specific transporters or ion channels expressed on the tubular epithelial membrane, leading to dysfunctional renal tubular reabsorption, secretion, and excretion. An in-depth understanding of the molecular genetic basis of hereditary renal tubular disease will help to understand the physiological function of renal tubules, the mechanism by which the kidney maintains water, electrolyte, and acid-base balance, and the relationship between the kidney and other systems in the body. Meanwhile, understanding these diseases also improves our understanding of the pathogenesis of hypokalemia, alkalosis and other related diseases and ultimately promotes accurate diagnostics and effective disease treatment. The present review summarizes the most common hereditary renal tubular diseases (Bartter syndrome, Gitelman syndrome, EAST syndrome and Liddle syndrome) characterized by hypokalemia and alkalosis. Further detailed explanations are provided for pathogenic genes and functional proteins, clinical manifestations, intrinsic relationship between genotype and clinical phenotype, diagnostic clues, differential diagnosis, and treatment strategies for these diseases.
Topics: Humans; Hypokalemia; Bartter Syndrome; Kidney Diseases; Alkalosis; Water
PubMed: 35994232
DOI: 10.1007/s40620-022-01428-4 -
Cureus May 2023Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we...
Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we describe a 21-year-old male who presented with myalgias, asthenia, general muscle weakness, and hypokalemia after receiving oral potassium supplementation for six months. Additional biochemical studies showed hypomagnesemia, metabolic alkalosis, and increased urinary potassium and magnesium excretion. Calcium urinary excretion was within the normal range, but 25-hydroxycholecalciferol levels were low. Systolic arterial hypertension was found, probably reflecting chronic hyperreninemic hyperaldosteronism. Genetic testing for mutations identified a pathogenic variant in homozygosity, which confirmed the Gitelman syndrome diagnosis. Treatment with chronic potassium and magnesium oral supplementation was started, as well as eplerenone and amiloride, with sustained correction of hypokalemia and hypomagnesemia.
PubMed: 37273382
DOI: 10.7759/cureus.38418