Metabolic Alkalosis Research Articles

Co-existence of non-classical congenital adrenal hyperplasia and Bartter syndrome complicated with central precocious puberty: A rare presentation

Congenital adrenal hyperplasia is an autosomal recessive disease marked by lack of enzymes required to produce specific hormones. About 90-95% of CAH are caused by steroid 21-hydroxylase deficiency and are the result of mutations in the CYP21A2 gene. Bartter syndrome is a rare autosomal recessive disorder characterized by hyperreninemia, metabolic alkalosis, hypokalaemia, and hypochloremia by activation of the RAS. The underlying renal abnormality results in electrolyte and acid-base imbalance abnormalities. We present a rare case of NCCAH coexisting with Bartter syndrome. A 5 years and 7 months old male was diagnosed with NCCAH at 20 days of life presented with fever and cold for one month, as well as recurrent UTIs for two weeks. General physical examination revealed carpopedal spasm, pubic hairs (+) with penile length (8.5 cm). Investigation revealed kaliuresis, hypercalciuria, metabolic alkalosis, hypokalaemia, and hypochloremia. X-ray of the left wrist revealed bone age as 9 years and genetic analysis was recommended. NCCAH with coexisting BS complicated with central precocious puberty was diagnosed. Symptomatic treatment was administered, and long-term steroid replacement advised. Congenital adrenal hyperplasia and Bartter syndrome is difficult to treat, and there is currently no complete cure. Close monitoring and prompt electrolyte replacement with symptomatic treatment are recommended.

Ultra-Low Dose Multi-Drug Quadruple Single-Pill Combination For Hypertension.

Respected Madam, Patients with hypertension require a multi-drug regimen to manage hypertension. But, multi-drug management may lead to patients’ lower cohesion to drugs and multiple adverse effects. (1) On the contrary a single pill containing four drugs (calcium channel blockers, beta-blockers, angiotensin II receptor blockers, and thiazide diuretics) of low dosages may deliver the same outcomes with lesser inauspicious effects. Current hypertension guidelines of the American Heart Association categorically recommend using a combination of four drugs in to manage and control hypertension, preferably in single-pill preparations. (2) Most patients remain on a single-drug therapy with insubordinate control, despite the recommendations that most require single-pill combination therapy of four drugs for blood pressure management (3) A recent randomized control trial demonstrated that a combination of four blood pressure-reducing agents in a single-pill at lower doses provided a simple, safe and potent treatment that improved the patient’s cohesion to the drug. The quadruple combination consists of four drugs: calcium channel blockers, beta-blockers, angiotensin II receptor blockers, and thiazide diuretics. Quadruple therapy is proven to have many benefits, namely higher efficacy, fewer adverse effects, and fast acting. It is found to be cost-effective as compared to monotherapy of multi-drugs. It is also known that patients taking high doses of multiple drugs to control blood pressure would be at higher risk of facing adverse effects such as bradycardia, hypokalemia, metabolic alkalosis, and constipation being the most common ones. In contrast, quadruple therapy consists of low dosages and it’s a combination of drugs to be taken together which helps the patient to surpass the adverse effects and effectively lower the blood pressure. It is also noted that quadruple therapy has proved effective in primary hypertension as a trial on a quadruple single-pill combination showed that the single-pill combination effectively reduced blood pressure in patients with stage 1 hypertension (4). In light of the above evidence, healthcare professionals should know the benefits of using a single-pill quadruple therapy for managing hypertension instead of traditional monotherapy. Moreover, additional studies should be performed on the effectiveness of using quadruple therapy.

Bartter Syndrome: A Systematic Review of Case Reports and Case Series.

Background and Objectives: Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods: Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ. Subsequently, the information was extracted in order to characterize the clinical presentation, laboratory results, treatment options, and follow-up of the patients with BS. Results: Overall, 118 patients, 48 case reports, and 9 case series (n = 70) were identified. Out of these, the majority of patients were male (n = 68). A total of 21 patients were born from consanguineous marriages. Most cases were reported from Asia (73.72%) and Europe (15.25%). In total, 100 BS patients displayed the genetic variants, with most of these being reported as Type III (n = 59), followed by Type II (n = 19), Type I (n = 14), Type IV (n = 7), and only 1 as Type V. The most common symptoms included polyuria, polydipsia, vomiting, and dehydration. Some of the commonly used treatments were indomethacin, potassium chloride supplements, and spironolactone. The length of the follow-up time varied from 1 month to 14 years. Conclusions: Our systematic review was able to summarize the clinical characteristics, presentation, and treatment plans of BS patients. The findings from this review can be effectively applied in the diagnosis and patient management of individuals with BS, rendering it a valuable resource for nephrologists in their routine clinical practice.

Novel Mutation of SLC26A3 Gene Observed in Congenital Chloride Diarrhea

Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by mutations in the solute carrier family 26 member 3 (<i>SLC26A3</i>) gene on chromosome 7q31. Affected neonates are vulnerable to dehydration, electrolyte imbalance in the form of hyponatremia, metabolic alkalosis, failure to thrive, or even death if left untreated. Genetic testing for mutations should be considered if the clinical diagnosis remains uncertain because early diagnosis and appropriate management are critical to the disease course in CLD. Several mutations have been reported in Korean patients with CLD, with the most common being the c.2063-1G>T mutation. Here, we report the case of a neonate with prenatally suspected CLD with confirmed novel mutations in the <i>SLC26A3</i> gene (c.2147C>G; p.Ala716Gly).

Severe Multifactorial Metabolic Alkalosis in the Emergency Department: A Case Report

BackgroundMetabolic alkalosis is an uncommon clinical entity resulting from a wide variety of underlying etiologies including gastrointestinal, renal, endocrine, and metabolic causes. It is a typically clinically silent condition; however, severe cases can be life-threatening, mandating both a systematic investigative approach and an early aggressive management strategy. Case ReportWe present a case of a 58-year-old man with severe, multifactorial metabolic alkalosis (pH 7.72, HCO3− 42 mmol/L, pCO2 31 mm Hg) resulting from refractory vomiting, severe hypokalemia (2.0 mmol/L), and hypoalbuminemia (albumin 20 g/L). Why Should an Emergency Physician Be Aware of This?Severe metabolic alkalosis is associated with significant morbidity and mortality. Clinicians need to be aware of the potential underlying causes in these cases, as well as how to delineate between chloride- and non-chloride-depleted states, which dictates initial treatment. We provide a pragmatic summary of the evaluation, pertinent investigations, and early management of these cases.

Bartter Syndrome: A Case Report

Background: Bartter's syndrome refers to a group of genetic disorders that affect the renal tubular system, which is responsible for reabsorbing various substances such as sodium, potassium, and chloride from the urine into the blood. This study aimed to present a clinical case related to Bartter syndrome.
 Case presentation: A 52-year-old male patient in the internal medicine department of Dr. M. Djamil General Hospital Padang with the main complaint of weakness in both legs increasing since 1 day ago. On laboratory examination, the patient found potassium 1.7 mmol/L, indicating hypokalemia. Renal function examination showed normal kidney function. Examination of blood gas analysis showed results of metabolic alkalosis. Examination of urine potassium obtained potassium levels of 22 mmol/day, urine osmolarity of 140 mOsm/kgH2O at serum osmolarity of 274 mOsm/kgH2O, with TTKG (transtubular potassium gradient) = 28. The patient was diagnosed with Bartter syndrome. Treatment is carried out by administering KSR tablets 3x600 mg orally while monitoring electrolytes regularly.
 Conclusion: This patient has hypokalemia, metabolic alkalosis, normal magnesium and calcium, and hypercalciuria. This patient is diagnosed with Bartter syndrome.

Acid-base and electrolyte evaluation in dogs with upper GI obstruction: 115 dogs (2015-2021).

Metabolic alkalosis, although uncommon in small animals, has been previously associated with gastrointestinal obstructions. Depending on the population and disease process evaluated, previous prevalence of metabolic alkalosis is reported as ranging from 2% to 45% in canine patients. The objective of this study was to determine the prevalence of metabolic alkalosis and other acid-base and electrolyte disorders in a cohort of dogs with a confirmed upper gastrointestinal obstruction. Electronic medical records were reviewed to identify dogs who presented for vomiting with evidence of an upper gastrointestinal obstruction from January 2015 to October 2021. Patients were enrolled only if a preoperative venous blood gas was obtained and analysed in house. Traditional acid-base analysis was utilised to determine an acid-base status before relieving the obstruction. When available, post-operative venous acid-base status was determined within 24 hours after surgery, and compared to preoperative results. A total of 115 dogs were included in the study. Twenty-five out of 115 (22%) dogs displayed either a simple metabolic alkalosis or a mixed acid-base disturbance before surgery. Twenty-seven out of 115 dogs (37%) had a normal acid-base status at entry. Seventy-one dogs had pre- and post-operative venous blood gas results available. Metabolic alkalosis was resolved in nearly all patients post-operatively, with no patients displaying a simple metabolic alkalosis. A mixed metabolic acidosis and respiratory alkalosis was the most common condition post-operatively, found in 25 of 71 (35%) dogs. Severe derangements of electrolytes were infrequent preoperatively (3/115; 2.6%). A majority of patients in this study exhibited hypokalaemia (64.4%), hypochloraemia (72.8%) and hyponatraemia (77.4%) on preoperative venous blood gases. Venous pH, Pv CO2 , bicarbonate and base excess were significantly higher preoperatively when compared to the post-operative results. This study found the prevalence of pre-operative metabolic alkalosis in dogs with a documented upper gastrointestinal obstruction to be lower than previously reported. Surgical or endoscopic alleviation of the upper gastrointestinal obstruction resulted in resolution of metabolic alkalosis in nearly all patients.

Safety of Citrate Anticoagulation in CKRT: Monocentric Experience of a Dynamic Protocol of Calcium Monitoring.

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity.

Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3

Bartter syndrome (BS) is a salt-losing hereditary tubulopathy characterized by hypokalemic metabolic alkalosis with secondary hyperaldosteronism. Confirmatory molecular diagnosis may be difficult due to genetic heterogeneity and overlapping of clinical symptoms. The aim of our study was to describe the different molecular findings in patients with a clinical diagnosis of classic BS. We included 27 patients (26 families) with no identified pathogenic variants in CLCNKB. We used a customized Ion AmpliSeq Next-Generation Sequencing panel including 44 genes related to renal tubulopathies. We detected pathogenic or likely pathogenic variants in 12 patients (44%), reaching a conclusive genetic diagnosis. Variants in SLC12A3 were found in 6 (Gitelman syndrome). Median age at diagnosis was 14.6 years (range 0.1–31), with no history of prematurity or polyhydramnios. Serum magnesium level was low in 2 patients (33%) but urinary calcium excretion was normal or low in all, with no nephrocalcinosis. Variants in SLC12A1 were found in 3 (BS type 1); and in KCNJ1 in 1 (BS type 2). These patients had a history of polyhydramnios in 3 (75%), and the mean gestational age was 34.2 weeks (SD 1.7). The median age at diagnosis was 1.8 years (range 0.1–6). Chronic kidney disease and nephrocalcinosis were present in 1 (25%) and 3 (75%) patients, respectively. A variant in CLCN5 was found in one patient (Dent disease), and in NR3C2 in another patient (Geller syndrome). Genetic diagnosis of BS is heterogeneous as different tubulopathies can present with a similar clinical picture. The use of gene panels in these diseases becomes more efficient than the study gene by gene with Sanger sequencing.

Hereditary forms of apparent mineralocorticoid excess (AME): Report of a further case and literature review

The syndrme of apparent mineralocorticoid excess (AME) is an extremly. rare autosomal recessive disorder. To date, more than 100 reported cases in the medical literature world-wide. It is caused by an impairment in the enzym 11-b-hydroxy steroid dehydrogenase (11-b-HSD) enzyme type 2, characterized by early onset hypertension, hypokalemia, metabolic alkalosis, low levels of seum renin and aldosterone. The majority of patients are usually have a low birth weight and failure to thrive (FTT). Nephrocalcinosis could be present. We describe an 11.5 year old girl, who presented in early infancy with poor growth, and not until a gene study done recently, which revealed a homozygous pathogenic variant in the HSD 11B2 gene c. 622 C >Tp. (Arg208 Cys ). This is consistent with the diagnosis of AME This emphasizes the importance of genetic testing in the diagnosis of AME. A high index of suspicion required in managing such patients. Increased awarness among health care professionals is needed to avoid potential health hazards.

Clinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome

Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS. Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS). Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene. Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6. Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.

The Relationship between Blood Gas Analysis Profile and the Outcome of Severe COVID-19 Patients

Coronaviruses commonly infect the respiratory tract, leading to severe pneumonia. Respiratory problems cause numerous acid-base disorders in 2019 Coronavirus Disease (COVID-19) patients. Several studies have explored laboratory biomarkers used in the management and prognosis of COVID-19 patients during this pandemic; however, only a few focused on blood gas analysis. Determine the blood gas analysis pattern and its association with the outcome of severe COVID-19 patients treated in the Intensive Care Unit (ICU). This retrospective cohort study used secondary data from patients with severe COVID-19 treated in the ICU of Hasanuddin University Hospital between January and December 2021. There was a higher number of male (58.8%) compared to female patients (41.5%), with a mean age of 62 years. Respiratory alkalosis was the most prevalent blood gas disorder (24.4%). Metabolic alkalosis was a blood gas disorder with the highest number of recovery/improvement outcomes (8 patients). There was no significant relationship between blood gas analysis results and the outcome of severe COVID-19. In addition, no specific pattern was found in the results of blood gas analysis. Respiratory alkalosis was the most frequent blood gas disorder detected in these patients.

Anti- N-MethyL-D-Aspartate Receptor Encephalitis in Children Infected with Herpes Simplex

Herpes Simplex Virus (HSV) is a common cause of infectious encephalitis in children, which can lead to severe neurological sequels. There is a new perspective suggesting that herpes simplex encephalitis plays an important role in triggering the synthesis of NMDA receptor antibodies. There have been no data on the incidence of anti-NMDA receptor encephalitis in Indonesia. Herpes simplex encephalitis was found in these patients as a risk factor for anti-NMDA receptor encephalitis. A 9-year-old male patient complained of seizures such as jerking of the right hand and smacking of the lips along with fever for 4 days before being admitted to the hospital. Complaints began with slurred speech and t inability of fingers to hold objects for the previous 8 days. From the physical examination, it was reported that the patient looked seriously ill, blood pressure was 110/80 mmHg, pulse was 117 beats per minute, the temperature was 38.5 C, and respiratory rate was 24 times per minute. Another physical examination was within normal limits. The results of a complete blood count at the time of initial treatment of patients showed mild leukocytosis due to a mild increase in monocytes, whereas blood gas and electrolyte analysis showed hypoventilation at the beginning of hospitalization in which mixed acid-base disturbance, respiratory acidosis, and metabolic alkalosis occurred. Analysis of cerebrospinal fluid in these patients showed mononuclear pleocytosis and the results of immunoserological test in serum indicated HSV1 and HSV2 infection and detected anti-NMDA receptor. Both clinical and laboratory findings in this study supported encephalitis. Herpes simplex virus infection can be a risk factor for patients suffering from anti-NMDA receptor encephalitis.

Forgotten but not gone: calcium‐alkali syndrome

AbstractBackgroundCalcium‐alkali syndrome (CAS) is characterised by hypercalcaemia, metabolic alkalosis, and renal injury. CAS has been a long‐standing concern but has fallen off the radar in recent times. However, supplementation of calcium and vitamin D for osteoporosis, and use of calcium based antacids for reflux has led to its resurgence as one of the leading causes for hypercalcaemia‐induced hospitalisations.AimWe present a case of CAS owing to excessive consumption of calcium carbonate in the presence of vitamin D.Clinical detailsAn 84‐year‐old woman presented to the hospital emergency room for the second time in 4 months after CAS was missed during the first admission. A history of significant (6–8 tablets daily) Quick‐Eze use (calcium carbonate), Gaviscon dual action antacid (calcium carbonate 32.5 mg/mL, sodium bicarbonate 21.3 mg/mL, sodium alginate 50 mg/mL) for reflux, and 2000 IU of vitamin D capsules for osteoporosis was the likely reason for CAS. COVID‐19 lockdown and the inability to fill esomeprazole scripts had increased the patient's reliance on over‐the‐counter treatments for reflux.OutcomesThe severe hypercalcaemia was treated using intravenous fluids and pamidronate, following which her serum calcium levels normalised, with resolution of symptoms.ConclusionThe effect of Quick‐Eze tablets on the development of hypercalcaemia should not be underestimated, especially in the presence of interacting medicines or supplements. This report highlights the importance of accurate history taking as the hypercalcaemia was missed during the patient's initial visit. Appropriate warning labels are warranted on Quick‐Eze tablets, as the current information is ambiguous, with no specific information on duration.

The concomitance of Gitelman syndrome with nephrocalcinosis in a case followed-up for primary biliary cirrhosis

Gitelman syndrome is a rare autosomal recessive renal tubular disease characterized by hypokalemia, metabolic alkalosis, and hypocalciuria. The syndrome develops as a result of various mutations in the SLC12A3 gene. This manuscript aims to highlight the association of Gitelman Syndrome with nephrocalcinosis in a 48-year-old female patient who presented with pain and cramps in the lower limbs.

Late Presentation of Bartter Syndrome as Refractory Hypokalemia

Bartter syndrome is a rare salt-wasting nephropathy characterized by sporadic or inherited genetic defects in transporters and channels in the thick ascending limb of the loop of Henle and distal tubule of Nephron leads to renal potassium wasting with hypokalemia, metabolic alkalosis, increased renin-angiotensin-aldosterone system, normal blood pressure. Most of the cases have been noted in the pediatric age group and adult-onset cases are very rare. Here we report an unusual case report of Bartter's syndrome in a 52 years old male patient.

Ectopic Cushing’s Syndrome as the First Presenting Sign of Small Cell Lung Carcinoma

A 67-year-old man with a history of hypertension, hyperlipidemia, coronary artery disease, and former smoking presented with fatigue, lower extremity edema, and a new tremor over the course of one month. Workup was notable for hypokalemia, metabolic alkalosis, and extremely elevated adrenocorticotropic hormone (ACTH) and cortisol levels. He was ultimately diagnosed with ectopic Cushing’s syndrome (CS) secondary to new metastatic small cell lung carcinoma. About 5-10% of CS cases are caused by ectopic ACTH production. The most commonly implicated malignancies are small cell lung cancer (SCLC) and neuroendocrine tumors, with SCLC accounting for up to three-fourths of cases. ACTH production is a poor prognostic sign in SCLC, associated with more extensive disease and decreased response to first-line treatment. Tumor-associated ACTH production is often so rapid that patients do not have time to develop classic Cushingoid physical exam findings, instead presenting with acute-onset hyperglycemia, pseudohyperaldosteronism, and generalized weakness. Prompt diagnosis and treatment are essential to improve outcomes.

Arterial Blood Gases and Acid-Base Regulation.

Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer system plays a pivotal role in maintaining acid-base homeostasis, and measurements of pH, PCO2, and HCO3 - are routinely used in the estimation of metabolic and respiratory disturbance severity. Hypoventilation and hyperventilation cause primary respiratory acidosis and primary respiratory alkalosis, respectively. Metabolic acidosis and metabolic alkalosis have numerous origins, that include alterations in acid or base intake, body fluid losses, abnormalities of intermediary metabolism, and renal, hepatic, and gastrointestinal dysfunction. The concept of the anion gap is used to categorize metabolic acidoses, and urine chloride excretion helps define metabolic alkaloses. Both the lungs and kidneys employ compensatory mechanisms to minimize changes in pH caused by various physiologic and disease disturbances. Treatment of acid-base disorders should focus primarily on correcting the underlying cause and the hemodynamic and electrolyte derangements that ensue. Specific therapies under certain conditions include renal replacement therapy, mechanical ventilation, respiratory stimulants or depressants, and inhibition of specific enzymes in intermediary metabolism disorders.

34-year-old female with acute onset quadriparesis and recurrent carpopedal spasm

Gitelman syndrome is an autosomal recessive condition also characterized by hypokalemic metabolic alkalosis, with hypocalciuria and hypomagnesemia

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading.

During acute base excess, the renal collecting duct β -intercalated cells ( β -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of β -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in β -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid-base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.