This composite educational image illustrates the clinical and diagnostic features of distal renal tubular acidosis (dRTA) associated with sensorineural hearing loss. (a) Data table showing results of a bicarbonate loading test, characterized by low urine-to-blood pCO2 gradient and positive urinary anion gap. (b) Renal ultrasound images of the left and right kidneys demonstrating medullary nephrocalcinosis, visualized as multiple hyperechoic foci within the renal pyramids. (c) Axial FIESTA (Fast Imaging Employing Steady-state Acquisition) cerebral MRI scan showing bilateral enlargement of the endolymphatic sacs (indicated by white arrows), a common finding in Pendred syndrome or dRTA with hearing loss. (d) Anatomical schematic of the inner ear, labeling the cochlea, vestibule, semicircular ducts, and endolymphatic duct. (e) Audiogram plot showing frequency (kHz) versus decibels (dB), depicting significant hearing impairment. The collection integrates metabolic laboratory data, diagnostic radiology (ultrasound and MRI), and functional audiological testing to present a comprehensive case of a hereditary renal-otological syndrome.

This pathophysiology diagram illustrates the cellular mechanism by which acidosis regulates MondoA transcriptional activity. The schematic is divided into two comparative states: 'Control' (blue background) and 'Acidosis' (red background). Key components include a mitochondrion, Hexokinase 2 (HK2), the MondoA protein, and metabolic intermediates glucose and glucose-6-phosphate (G6P). Under control conditions, mitochondrial ATP (mtATP) levels are low, and HK2 is bound to the outer mitochondrial membrane. Glucose is converted to G6P by HK2, resulting in basal MondoA interaction. In the 'Acidosis' state, a shift in pH drives a significant increase in mtATP production. This high mtATP concentration facilitates enhanced HK2 enzymatic activity at the mitochondrial surface, leading to increased production of G6P. The elevated G6P levels trigger MondoA to undergo nuclear localization and increased transcriptional activity, as indicated by a large upward arrow toward the nucleus. This diagram demonstrates how metabolic sensing of mitochondrial energy charge and cytoplasmic glucose levels are integrated via HK2 to control gene expression under conditions of metabolic stress or altered pH.

This physiological diagram illustrates the metabolic and inflammatory response during Blood Flow Restriction (BFR) training on the human thigh. A compression cuff is shown positioned on the proximal thigh, labeled with an upward arrow and the text 'Ischemic/Hypoxic' to indicate the restriction of blood flow and oxygen. Within the quadriceps region, multiple 'H+' symbols denote an increase in hydrogen ion concentration, reflecting intramuscular acidosis. On the distal thigh, a group of metabolic markers summarizes the endocrine and inflammatory cascade: '[La]' (lactate) and 'GH' (growth hormone) are associated with an upward arrow pointing toward 'IL-6' (interleukin-6), indicating an increase in these pro-inflammatory/hypertrophic signals. Conversely, 'Glycogen' is shown with a downward arrow, representing substrate depletion. The graphic serves as a conceptual model for exercise physiology, demonstrating how localized metabolic stress, hypoxia, and inflammatory cytokine production contribute to muscle hypertrophy during low-intensity strength training with vascular occlusion.

<table><thead><tr><th>Practice Point 1.4.1. Use loop diuretics as first-line therapy for treatment of edema in the nephrotic syndrome</th><th>• Twice daily dosing preferred over once daily dosing; daily dosing may be acceptable for reduced GFR • Increase dose of loop diuretic to cause clinically significant diuresis or until maximally effective dose has been reached • Switch to longer acting loop diuretic such as bumetanide or torsemide/torasemide if concerned about treatment failure with furosemide, or if concerned about oral drug bioavailability</th></tr></thead><tbody><tr><td>Practice Point 1.4.2. Restrict dietary sodium intake</td><td>• Restrict dietary sodium to <2.0 g/d (<90 mmol/d)</td></tr><tr><td>Practice Point 1.4.3. Use loop diuretics with other mechanistically different diuretics as synergistic treatment of resistant edema in the nephrotic syndrome</td><td>• All thiazide-like diuretics in high doses are equally effective. None is preferred. • Thiazide diuretics, administered with an oral or i.v. loop diuretic, will impair distal sodium reabsorption and improve diuretic response • Amiloride may provide improvement in edema/hypertension, and counter hypokalemia from loop or thiazide diuretics • Acetazolamide may be helpful for the metabolic alkalosis of diuresis • Spironolactone may provide improvement in edema/hypertension, and counter hypokalemia from loop or thiazide diuretics</td></tr><tr><td>Practice Point 1.4.4. Monitor for adverse effects of diuretics</td><td>• Hyponatremia with thiazide diuretics • Hypokalemia with thiazide and loop diuretics • Impaired GFR • Volume depletion, especially in pediatric/elderly patients • Hyperkalemia with spironolactone and eplerenone especially if combined with RAS blockade</td></tr><tr><td>Practice Point 1.4.5. Strategies for diuretic-resistant patient</td><td>• Amiloride • Acetazolamide • i.v. loop diuretics (bolus or infusion) alone • i.v. loop diuretics in combination with i.v. albumin • Ultrafiltration • Hemodialysis • Amiloride may reduce potassium loss and improve diuresis. Acetazolamide may help to treat metabolic alkalosis but is a weak diuretic</td></tr></tbody></table>

This pathophysiology diagram illustrates the metabolic mechanisms and survival outcomes of hepatocellular carcinoma (HCC) cells under three different experimental conditions. Panel A (Normal condition) shows healthy cellular metabolism where glucose enters the cell, undergoing glycolysis to produce ATP and pyruvate. Pyruvate enters the mitochondria, powering the electron transport chain (eTC) for further ATP generation, resulting in cell survival. Panel B (Only sorafenib/OA treatment) depicts the effect of electron transport chain inhibitors (sorafenib or oligomycin/antimycin). This treatment causes mitochondrial membrane potential (MMP) loss and impairs mitochondrial ATP production. However, glycolysis remains active, generating sufficient ATP to support PINK1-mediated mitophagy. Mitophagy eliminates damaged mitochondria and prevents reactive oxygen species (ROS) accumulation, allowing continued cell survival. Panel C (Glucose restriction combined with sorafenib/OA treatment) demonstrates the synergistic effect of inhibiting both energy pathways. Glucose restriction abolishes glycolysis-derived ATP, which in turn prevents the activation of mitophagy despite mitochondrial damage. This leads to excessive ROS accumulation, extensive mitochondrial failure, and clinical cell death. This diagram highlights the importance of targeting dual metabolic pathways in HCC therapy.

<table><tr><td>Practice Point 1.4.1. Use loop diuretics as first-line therapy for treatment of edema in the nephrotic syndrome</td><td>• Twice daily dosing preferred over once daily dosing; daily dosing may be acceptable for reduced GFR<br>• Increase dose of loop diuretic to cause clinically significant diuresis or until maximally effective dose has been reached<br>• Switch to longer acting loop diuretic such as bumetanide or torsemide/torasemide if concerned about treatment failure with furosemide, or if concerned about oral drug bioavailability</td></tr><tr><td>Practice Point 1.4.2. Restrict dietary sodium intake</td><td>• Restrict dietary sodium to <2.0 g/d (<90 mmol/d)</td></tr><tr><td>Practice Point 1.4.3. Use loop diuretics with other mechanistically different diuretics as synergistic treatment of resistant edema in the nephrotic syndrome</td><td>• All thiazide-like diuretics in high doses are equally effective. None is preferred.<br>• Thiazide diuretics, administered with an oral or i.v. loop diuretic, will impair distal sodium reabsorption and improve diuretic response<br>• Amiloride may provide improvement in edema/hypertension, and counter hypokalemia from loop or thiazide diuretics<br>• Acetazolamide may be helpful for the metabolic alkalosis of diuresis<br>• Spironolactone may provide improvement in edema/hypertension, and counter hypokalemia from loop or thiazide diuretics</td></tr><tr><td>Practice Point 1.4.4. Monitor for adverse effects of diuretics</td><td>• Hyponatremia with thiazide diuretics<br>• Hypokalemia with thiazide and loop diuretics<br>• Impaired GFR<br>• Volume depletion, especially in pediatric/elderly patients<br>• Hyperkalemia with spironolactone and eplerenone especially if combined with RAS blockade</td></tr><tr><td>Practice Point 1.4.5. Strategies for diuretic-resistant patient</td><td>• Amiloride<br>• Acetazolamide<br>• i.v. loop diuretics (bolus or infusion) alone<br>• i.v. loop diuretics in combination with i.v. albumin<br>• Ultrafiltration<br>• Hemodialysis<br>• Amiloride may reduce potassium loss and improve diuresis. Acetazolamide may help to treat metabolic alkalosis but is a weak diuretic</td></tr></table>