We report a rare case of a monogenic form of hypertension where a boy in early childhood presented with a 2-day history of right-sided facial palsy. Severe hypertension was evident with signs of end-organ damage. This report aims to highlight the diagnostic process when a common presentation, such as facial palsy, uncovers a serious and rare underlying condition that demands urgent multidisciplinary care. Further workup revealed that the patient had hypokalaemic metabolic alkalosis with low serum renin and aldosterone levels. His urinary steroid profile was suggestive of Apparent Mineralocorticoid Excess. A homozygous autosomal recessive variant in the hydroxysteroid 11-beta dehydrogenase 2 gene confirmed a diagnosis of 11β-hydroxysteroid dehydrogenase type 2 deficiency. The syndrome has fewer than one hundred cases documented to date, with reversal of the mineralocorticoid effect as the primary treatment. This case highlights the importance of a step-by-step approach to paediatric hypertension and the need for an early urinary steroid profile.

Methanol intoxication causes metabolic acidosis, organ injury, and death; renal injury predicts adverse outcomes. Ethanol and fomepizole were compared in a methotrexate-pretreated rat model of methanol intoxication. Thirty male Wistar rats were allocated to five groups: Control, methotrexate (MTX), MTX + Methanol, MTX + Methanol + Fomepizole, and MTX + Methanol + Ethanol (n = 6 per group). MTX was administered by oral gavage at 0.3 mg/kg/day on days 1-7. The three methanol-exposed groups received 3 g/kg methanol by oral gavage on day 8. Fomepizole was administered intraperitoneally at 15 mg/kg 4 h after methanol administration, followed by 10 mg/kg at 12, 24, and 36 h. Ethanol was administered once by oral gavage at 0.5 g/kg 4 h after methanol administration. Samples were collected on day 10. No primary outcome was prospectively designated. Renal function, kidney homogenate injury, inflammatory biomarkers, blood-derived redox-related biomarkers, and histopathological findings were assessed. Analysis of variance (ANOVA) revealed significant group differences in kidney-homogenate cystatin C (p = 0.003), interleukin-6 (IL-6; p = 0.013), kidney injury molecule-1 (KIM-1; p = 0.017), serum urea (p = 0.017), and serum creatinine (p < 0.001). Duncan post hoc testing showed lower values for these parameters in both antidote groups than in the MTX + Methanol group. No significant biochemical differences were identified between the two antidote groups. Histopathological scores were lower in the antidote groups. Although fomepizole showed a more favorable descriptive pattern, the findings do not establish its superiority over ethanol. Variance heterogeneity, multiple testing, unequal antidote regimens, the absence of toxicokinetic and acid-base measurements, and short follow-up limit interpretation. Future studies should include direct measurements of methanol and formate, renal cytosolic alcohol dehydrogenase activity, correlations with renal biochemical outcomes, longer follow-up periods, and comparable antidote regimens.

With advances in nanotechnology, nanomedicines that combine diagnostic and therapeutic functions have emerged, offering advantages such as early, precise diagnosis and more reliable therapeutic outcomes than conventional treatments. Despite these benefits, most nanomedicines require intravenous or other invasive administration routes, leading to safety and patient compliance concerns that hinder clinical translation. Oral delivery represents an ideal drug administration method due to its convenience and the protective barrier provided by the gastrointestinal tract, which enhances safety and compliance. However, challenges such as low drug solubility, limited permeability of the gastrointestinal barrier, and the harsh acid-base and enzymatic environment of the gastrointestinal tract significantly impact the efficacy and application of oral nanomedicines. Additionally, reduced bioavailability resulting from first-pass hepatic metabolism after gastrointestinal absorption through the venous plexus presents a major technical obstacle for orally administered nanomedicines. This review introduces design strategies for oral nanomedicines using a function-oriented approach and summarizes the characteristics of various nanomedicine types based on structural similarities and differences. Several representative oral nanomedicines developed in recent years are highlighted, with a focus on their applications to specific diseases. The review also discusses the potential and current limitations of oral nanomedicines that must be addressed to facilitate future clinical translation. The primary objective is to provide a comprehensive analysis of oral drug administration from multiple perspectives and to offer valuable insights for clinical application.

Alkalosis is an abnormal pathophysiological condition characterized by the buildup of excess base or alkali in the body. It results in an abnormally high serum pH (arterial pH greater than 7.45), which is termed alkalemia and forms one end of the spectrum of acid-base disorders. There is generally a loss of hydrogen ions (H) or an excess of bicarbonate ions (OH), and multiple factors can cause either of these. In general, alkalosis is less life-threatening than acidosis, but severe electrolyte derangements can accompany alkalosis due to transcellular shifts, potentially resulting in rare but severe clinical disorders. Alkalosis can be either respiratory or metabolic in origin, but metabolic alkalosis is far more common than respiratory causes.[1]

Calcium is an essential element for normal physiologic function. Normal serum calcium is maintained within a close range of 8.4 to 10.4 mg/dL, and acute or severe changes can result in serious cardiac, musculoskeletal, and neurologic consequences. Normal calcium levels are maintained by interactions of parathyroid hormone and vitamin D. Parathyroid hormone regulates calcium levels via bone resorption, renal calcium reabsorption, and enhanced calcium absorption in the small intestine. Causes of hypocalcemia include hypoparathyroidism (often postsurgical), severe chronic kidney disease, and vitamin D deficiency. Laboratory testing for serum parathyroid hormone, kidney function, vitamin D metabolites, and serum phosphorus can help differentiate among causes. Acutely symptomatic patients require inpatient treatment with intravenous calcium gluconate, cardiac monitoring, and correction of hypomagnesemia. Hypercalcemia is most often due to primary hyperparathyroidism or malignancy. In the evaluation, hypercalcemia should first be confirmed by measurement of ionized calcium or repeat measurement of total serum calcium and correction for albumin. Obtaining a serum parathyroid hormone level is the next step. Asymptomatic, chronic mild hypercalcemia is often caused by primary hyperparathyroidism, which can be observed or treated surgically. Patients with severe hypercalcemia may have profound dehydration and require inpatient treatment with intravenous fluids, bisphosphonates, and calcitonin.

Maintaining a normal physiologic acid-base balance is essential for the functioning of every organ system in the body. The renal and pulmonary systems are the primary regulators of acid-base balance. There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A systematic approach to evaluation is critical to identify potential etiologies. A history, physical examination, metabolic profile, and arterial blood gas measurement provide a full assessment of acid-base status. However, availability of arterial blood gas measurements is usually limited outside of inpatient and emergency department settings. Calculation of an anion gap is a crucial first step for evaluating laboratory test results. Changes in serum pH, Pco2, serum bicarbonate concentration, and anion gap suggest the primary disorder, and predictable compensatory changes indicate whether a secondary acid-base disturbance is present. Mixed acid-base disorders involving the renal and pulmonary systems can occur, underscoring the importance of a systematic approach to evaluation. In the outpatient setting, primary care physicians play a vital role in identifying and treating these disorders based on initial evaluation. Prompt recognition and management of acid-base disorders can help prevent morbidity and mortality.

In adult humans, albumin is the most abundant plasma protein, with a concentration of 35 to 50 g/L. Albumin represents 50% to 60% of the total protein content of plasma, with globulins comprising most of the remaining protein. The protein consists of a single peptide chain of 585 amino acids arranged in a globular structure. The molecular weight of albumin is approximately 66 kDa, and its half-life is 14 to 21 days. Albumin is exclusively synthesized by the liver, initially as preproalbumin and subsequently as proalbumin, which is converted to albumin in the Golgi apparatus. Albumin then leaves the hepatocyte and enters the systemic circulation. The albumin synthesis rate is approximately 10 to 15 g/d, and around 40% remains in the circulation, whereas the remainder moves from the intravascular to the interstitial space. Factors that stimulate albumin synthesis include hormones such as insulin and growth hormone. Conversely, proinflammatory mediators, including IL-6, IL-1, and tumor necrosis factor, may inhibit albumin production. During fetal life, α-fetoprotein, produced by the liver and yolk sac, is the most abundant plasma protein. α-Fetoprotein is thought to be the fetal counterpart of albumin, and the genes encoding both proteins are located near each other on chromosome 4. Approximately 100 variant forms of albumin have been described. Albumin is lost into extravascular spaces, where it undergoes degradation. Approximately 40% to 60% of albumin degradation occurs in the skin and skeletal muscle. In healthy individuals, albumin loss through the gastrointestinal tract and kidneys is minimal. Albumin has several physiological roles. One of its most important functions is maintaining oncotic pressure within the vascular compartments, thereby preventing fluid leakage into the extravascular spaces. Albumin accounts for approximately 80% of the colloid osmotic pressure. Additionally, albumin functions as a low-affinity, high-capacity carrier of several endogenous and exogenous compounds, serving as a depot and transporter for these substances. Binding compounds to albumin may reduce their toxicity, including that of unconjugated bilirubin in neonates and certain medications. Moreover, albumin binds at least 40% of circulating calcium and transports hormones such as thyroxine, cortisol, and testosterone. Albumin is the primary carrier of fatty acids and has significant antioxidant properties. The protein also helps maintain acid-base balance by acting as a plasma buffer. Albumin is used as a marker of nutritional status and disease severity, particularly among patients with chronic illness or critical illness. Normal innate and adaptive immune responses also rely on albumin. Renal and gastrointestinal tract losses may account for approximately 6% and 10%, respectively, of albumin loss in healthy individuals. A serum albumin level less than the reference range is termed hypoalbuminemia. The following sections review the causes and diagnosis of hypoalbuminemia.

Phosphate accounts for about 0.6% of body weight at birth and about 1% of body weight in adults. This anion is essential for the performance of many essential human cellular processes, including energy metabolism and cell signaling; it is also a key component of the phospholipid bilayer and nucleic acids structure. In addition, phosphate is responsible for maintaining acid-base balance within the cells, functioning of the nervous system and preserving bone integrity. Normal serum phosphate levels change throughout life, varying from the neonatal period, through adolescence, and stabilizing at adult values by the end of puberty. Serum phosphate homeostasis is maintained through dietary intake, intra- and intercellular shifts, and excretion/absorption/reabsorption processes mediated by Fibroblast Growth Factor 23, parathyroid hormone, and 1,25-(OH)2D3. Within this homeostatic network, dietary sources and current population-based intake data highlight a widespread oversupply in modern diets that can influence chronic disease outcomes. Ultimately, alterations in serum phosphate concentrations lead to numerous pathological conditions, both congenital and acquired. These conditions may involve either hypo- or hyperphosphatemia, each characterized by a wide spectrum of clinical manifestations, some of which primarily affect the musculoskeletal system. Starting from this evidence, the primary purpose of this review is to examine the phosphate-related pathological conditions from biological-molecular and clinical perspectives, while also considering targeted nutritional and clinical strategies for managing phosphate balance. Algorithms for management and differential diagnosis are also considered, thus providing a recent overview of a medical field that is becoming increasingly important for clinicians.

Acid-base homeostasis is essential for cellular and systemic function. Its maintenance requires tightly regulated compensatory mechanisms capable of correcting disturbances that threaten physiological balance, as dysregulation can be life-threatening. When a primary metabolic disturbance occurs and alters bicarbonate concentration (HCO3), the main compensatory mechanism is a respiratory response that adjusts the partial pressure of carbon dioxide (PCO2). Conversely, a primary respiratory disturbance, whether acute or chronic, leads to changes in PCO2, and compensatory response occurs through a metabolic response that modifies HCO3[-] levels. Mixed disturbances are also common and may represent a diagnostic challenge in clinical practice. To assess acid-base status, clinical laboratories use blood gas analyzers, which provide information to identify metabolic, respiratory, or mixed disorders. Several formulas are available to estimate the compensatory response according to the primary disturbance. These formulas take into account parameters such as PCO2, actual bicarbonate (HCO3[-]c), and standard base excess, all of which are reported in blood gas analysis. The implementation of expert rules within Laboratory Information Systems or Clinical Decision Support tools, which automatically apply these formulas, could facilitate the evaluation of whether compensatory response is appropriate or if a mixed disorder is present, potentially improving the diagnostic accuracy of blood gas analysis and adding value to laboratory reports. This review summarizes the main approaches described in the literature and proposes a standardized procedure to incorporate the study of compensatory mechanisms into the interpretation of acid-base disorders, with the aim of improving diagnostic accuracy and supporting clinicians in patient management.

Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that catalyze the reversible conversion of carbon dioxide and water into bicarbonate and protons, contributing to acid-base balance, pH regulation, and ion transport. Among human cytosolic isoforms, carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) are abundant and clinically relevant, yet their distinct roles are often obscured within broader discussions of the CA family. This narrative review evaluates CA I and CA II as biomarkers and therapeutic targets in glaucoma, atherosclerosis and vascular calcification, anemia, epilepsy, Alzheimer's disease, obstructive sleep apnea, obesity-related metabolic dysfunction, and selected cancers. CA II emerges as the more established pharmacological target, particularly in glaucoma, with acetazolamide and sultiame showing therapeutic potential in obstructive sleep apnea and possible contributions to epilepsy and neurodegeneration through pH regulation, bicarbonate-dependent signaling, and mitochondrial function. CA I instead appears more valuable as a disease-associated biomarker, especially in disorders involving erythrocyte turnover, inflammation, anemia, and malignancy, though circulating CA I may be confounded by hemolysis and altered erythrocyte dynamics. Clinical translation requires isoform-selective modulators, tissue-targeted delivery, standardized biomarker assays, and mechanistic models distinguishing primary CA involvement from secondary disease-related changes.