NORMAL RENAL PHYSIOLOGY AND DIURETICS (MedStudy)

Key concepts and terms from the Renal Physiology and Diuretics sections to reinforce understanding and prepare for exams.

Glomerulus

A highly specialized capillary tuft within Bowman's capsule where blood filtration occurs, forming the ultrafiltrate that becomes renal tubular filtrate.

Glomerular filtration barrier components

Endothelial cells, glomerular basement membrane, and slit diaphragms between podocyte foot processes that together filter plasma.

Proximal convoluted tubule bicarbonate reabsorption

The PCT reabsorbs about 90% of filtered bicarbonate (HCO3-); carbonic anhydrase catalyzes the conversion of CO2 and H2O to H2CO3, then to HCO3- and H+, with HCO3- returned to blood.

Acetazolamide (carbonic anhydrase inhibitor)

Drug that inhibits proximal tubule carbonic anhydrase, causing bicarbonate wasting and a normal anion gap metabolic acidosis.

Loop of Henle function

Descending limb concentrates tubular fluid by water reabsorption; ascending limb actively reabsorbs NaCl and is water-impermeable.

Loop diuretics

Furosemide, bumetanide, and ethacrynic acid inhibit NaCl reabsorption in the thick ascending limb, causing brisk diuresis and increased Ca2+ excretion; beware sulfa allergy with some agents.

Furosemide and calcium

Loop diuretics increase Ca2+ excretion (calciuresis) and can be used to treat hypercalcemia alongside saline hydration.

Distal convoluted tubule function

Na+ is actively reabsorbed; H+ (as ammonium or phosphate) and K+ are secreted, driven by the Na+/K+ gradient and aldosterone.

Aldosterone effects in distal nephron

Promotes Na+ reabsorption and K+ and H+ excretion, contributing to metabolic alkalosis when in excess.

Collecting duct and ADH

ADH increases water permeability via aquaporin channels, concentrating urine in the collecting duct when present.

Antidiuretic hormone (ADH)

Neurohypophysial hormone (vasopressin) that regulates water reabsorption in the late distal tubule and collecting duct.

Spironolactone

Aldosterone antagonist (K+-sparing diuretic) that can cause hyperkalemia and acidosis by blocking aldosterone’s effects.

Triamterene and amiloride

K+-sparing diuretics that inhibit Na+ entry in distal tubular cells, reducing K+ and H+ excretion.

Thiazide diuretics

Inhibit Na+/Cl- reabsorption in the early distal tubule; less effective at CrCl <30 mL/min; decrease Ca2+ excretion; synergize with loop diuretics.

Proximal tubule calcium reabsorption

The proximal tubule reabsorbs about 60% of filtered Ca2+.

Hypercalcemia management in acute settings

Vigorous saline hydration to increase Filtration and calciuresis; loops may be added, with calcitonin and bisphosphonates preferred for persistent hypercalcemia.

Hypocalcemia management basics

Correct with calcium supplementation (oral then IV if needed); measure ionized Ca2+ for accuracy; correct underlying causes.

Renal testing (urinalysis) components

Macroscopic exam, chemical dipstick analysis, and microscopic sediment to evaluate kidney disease, infection, diabetes, and other disorders.

Orthostatic proteinuria

Benign proteinuria that occurs when upright but is absent in the first morning urine; >0.2 mg/m2/day protein/creatinine ratio suggests persistent pathology.

Glomerular filtration rate (GFR)

A measure of overall kidney function; normal ~120 mL/min/1.73 m2; neonates ~20 mL/min/1.73 m2; eGFR is estimated from serum creatinine or cystatin C.

Serum creatinine (Cr)

A common marker of kidney function influenced by muscle mass and age; can be altered by drugs and conditions affecting secretion.

Cystatin C

An alternative kidney function marker not dependent on muscle mass; used with Cr to estimate GFR.

BUN:creatinine ratio (BUN:Cr)

A ratio >20:1 suggests prerenal azotemia due to decreased renal perfusion or volume depletion.

Fractional excretion of sodium (FENa)

Percent of filtered Na+ excreted in urine;

Urine anion gap (UAG)

UAG = Na+ + K+ - Cl-; helps distinguish GI bicarbonate losses (negative UAG) from renal ammonium excretion defects (positive UAG) in NAGMA.

Anion gap (AG)

AG = Na+ - (Cl- + HCO3-); normal ~3-11 mEq/L; elevated AG indicates unmeasured anions (HAGMA). Albumin correction is needed if albumin is abnormal.

Albumin correction of anion gap

AG must be corrected for hypo- or hyperalbuminemia; estimated correction is adding 2.5 mEq/L to AG for each 1 g/dL drop in albumin.

Osmolality vs osmolal gap

Osmolality is the concentration of osmotically active particles; OG = measured osmolality − calculated osmolality (OsmCalc). A high OG suggests toxic alcohol ingestion.

Osmol calc formula

OsmCalc ≈ 2[Na+] + BUN/2.8 + glucose/18 (simplified as 2[Na+] + BUN/3 + glucose/20 for ease).

Osmol gap (OG) significance

OG > ~25 mOsm/kg often indicates toxic alcohols (e.g., methanol, ethylene glycol).

Acid-base disorders (overview)

Disorders with abnormal pH due to primary metabolic (HCO3-), or primary respiratory (PaCO2) disturbances; compensation by the opposite system; AG and OG help characterize etiology.

MedStudy 4-Step Method

A practical 4-step approach to acid-base problems: Step 1 determine pH, Step 2 identify the primary disorder, Step 3 assess compensation and mixed disorders, Step 4 calculate the anion gap.

High anion gap metabolic acidosis (HAGMA)

Metabolic acidosis with increased unmeasured anions; common causes include ketoacidosis, lactic acidosis, uremia, and toxins (MUDPILES).

Winters formula

Prediction for respiratory compensation in metabolic acidosis: expected PaCO2 ≈ (1.5 × HCO3-) + 8 ± 2; use the full Winters formula when HCO3- < 10 mEq/L.

Normal anion gap metabolic acidosis (NAGMA)

Metabolic acidosis with a normal AG; typically due to bicarbonate loss (GI losses or RTA) or renal ammonium excretion defects.

Metabolic alkalosis chloride-responsive

Alkalosis that improves with volume repletion and IV saline; low urinary Cl- (<20 mEq/L) indicates chloride-responsive cause (e.g., vomiting, diuretic use).

Metabolic alkalosis chloride-resistant

Alkalosis not corrected with saline; often due to excess aldosterone activity (e.g., primary hyperaldosteronism). Urinary Cl- >20 mEq/L favors chloride-resistant causes.

MUDPILES

Mnemonic for common causes of high anion gap metabolic acidosis: Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates.

Toxic alcohols and osmolality

Methanol and ethylene glycol cause high OG and high AG; fomepizole inhibits alcohol dehydrogenase; dialysis may be needed in severe cases.

HUS (hemolytic-uremic syndrome)

Triad of microangiopathic hemolytic anemia, thrombocytopenia, and AKI, commonly following STEC (STEC-HUS) diarrhea; supportive care and dialysis as needed.

Glomerulonephritis (GN) overview

Inflammation/injury to glomeruli; includes APSGN, MPGN, IgA nephropathy, SLE nephritis; complements levels help differentiate etiologies.

Acute postinfectious GN (APSGN)

Common pediatric GN after nephritogenic Streptococcus infection; low C3 with normal C4; treated supportively; antibiotics eradicate infection but do not prevent APSGN.

IgA nephropathy

Most common primary GN worldwide; recurrent gross hematuria with URI; C3 usually normal; biopsy shows IgA and C3 in mesangium.

IgA vasculitis nephritis (HSP nephritis)

Renal involvement in IgA vasculitis (Henoch–Schönlein purpura); IgA deposition with similar pathology to IgA nephropathy; often self-limited but may require steroids.

Anti-GBM disease (Goodpasture)

Anti-glomerular basement membrane antibodies causing RPGN with or without pulmonary hemorrhage; treated with plasmapheresis, steroids, and immunosuppression.

ANCA-associated GN

Pauci-immune crescentic GN including GPA, MPA, and EGPA; diagnosed with ANCA serology; treated with immunosuppression; often severe with renal involvement.

RPGN (crescentic GN)

Rapidly progressive GN characterized by crescents in glomeruli; requires aggressive immunosuppression and sometimes plasmapheresis.

Nephrotic syndrome (overview)

Heavy proteinuria (>1 g/m2/day or protein/Cr ratio >2), hypoalbuminemia, edema, and often hyperlipidemia; commonly due to Minimal Change Disease in children.

Minimal Change Disease (MCD)

Most common cause of pediatric nephrotic syndrome; usually idiopathic; excellent response to steroids.

FSGS (focal segmental glomerulosclerosis)

Glomerular disease often steroid-resistant; linked to obesity, HIV, hypertension; may require immunosuppression and ACE inhibitors/ARBs.

Membranous nephropathy in children

Immune complex deposition in GBM; less common in kids and often secondary to infections or medications; usually nephrotic.

ARPKD vs ADPKD (overview)

ARPKD presents in infancy with Potter facies and hepatic fibrosis; ADPKD is usually adult-onset with bilateral renal cysts and risk of berry aneurysms.

Nephronophthisis (NPH)

Tubulointerstitial kidney disease leading to ESRD in childhood; polyuria/polydipsia and growth delay; associated extrarenal features.

Tuberous sclerosis complex (TSC) and kidneys

AD disease with renal angiomyolipomas and cysts; risk of hemorrhage; mTOR inhibitors used for lesions.

Medullary sponge kidney

Rare congenital disorder with ectasia of collecting ducts in the medulla; UTIs, hematuria, and stones.

Nail-patella syndrome

AD disorder with nephropathy (often benign) and nail/patella abnormalities due to LMX1B mutation.

Renal tubular acidosis (RTA) types I, II, IV

Metabolic acidosis with normal AG; Type 1 distal has high urine pH and hypokalemia; Type 2 proximal has low urine pH and Fanconi features; Type 4 hypoaldosteronism has hyperkalemia.

Distal RTA (Type 1)

Impaired ammoniagenesis with high urine pH and hypokalemia; positive urine anion gap indicates ammonium excretion defect.

Proximal RTA (Type 2)

Impaired proximal bicarbonate reabsorption with bicarbonate wasting; urine pH typically <5.5; often part of Fanconi syndrome.

Type 4 RTA (hypoaldosteronism)

Hyperkalemic, mild NAGMA due to reduced aldosterone activity or resistance; common in obstructive uropathy or interstitial disease.

Hyponatremia management in children

Determine tonicity; treat hypotonic hyponatremia based on volume status; symptomatic hyponatremia treated with hypertonic saline; correct gradually to avoid osmotic demyelination.

Hypernatremia management

Treat with isotonic saline to restore volume, then give free water to correct deficit gradually to avoid cerebral edema.

Maintenance fluids in children (AAP 2018)

Recommendation to use isotonic maintenance fluids (e.g., D5NS, D5LR) to reduce iatrogenic hyponatremia; adjust volumes by weight and electrolyte needs.

Hypovolemic hyponatremia

Volume depletion with Na+ loss greater than water loss; commonly due to vomiting, diarrhea, diuretics; treat with isotonic saline.

Euvolemic hyponatremia (SIADH)

Hyponatremia with normal total body water; often due to SIADH; treatment includes fluid restriction and addressing underlying cause.

Hypervolemic hyponatremia

Water and Na+ retention with more water than Na+; edema states (HF, cirrhosis, nephrotic syndrome); treat with fluid restriction and loop diuretics.

3% saline bolus for hyponatremia

Hypertonic saline (3%) given in boluses (3-5 mL/kg up to 100 mL) for severe symptomatic hyponatremia to rapidly raise Na+ by ~2-3 mEq/L.

Osmotic demyelination syndrome (ODS) risk

Over-aggressive correction of chronic hyponatremia (>10 mEq/L/24h) can cause brain demyelination; monitor Na+ closely during correction.

Hypernatremia neurological risk

Hypernatremia can cause cerebral edema if corrected too rapidly; gradual correction is essential.

Hyperkalemia ECG progression

Peaked T waves, lengthening PR and QRS, loss of P wave with sine-wave pattern; requires urgent stabilization with IV calcium.

Hyperkalemia treatment sequence

Stabilize membranes (IV Ca2+), shift K+ into cells (insulin + glucose, bicarbonate, albuterol), remove K+ (diuretics, resins, dialysis) and address underlying causes.

Hypokalemia ECG changes

U waves and flattened T waves; may cause muscle weakness and arrhythmias; replace K+ and treat underlying causes.

Sodium polystyrene sulfonate (SPS) caution

Resin used to remove K+; can cause colonic necrosis, especially with sorbitol or ileus; not monotherapy for hyperkalemia.

Desmopressin (DDAVP) for diabetes insipidus

Intranasal or oral desmopressin used to treat central DI; monitor for hyponatremia during therapy.

Diabetes insipidus (DI) types

Central DI (low ADH) vs nephrogenic DI (renal insensitivity); differentiate with water deprivation test and vasopressin administration.

Boys vs girls in Alport syndrome

X-linked Alport is more common in boys with progressive nephritis; females may have milder or later manifestations.

Hepatic fibrosis in ARPKD

Universal hepatic fibrosis with portal hypertension; Caroli disease may develop and increase risk of cholangitis.

Vascular and glomerular diseases in children

Hypertension can accompany GN and nephrotic syndromes; evaluation includes BP monitoring and imaging as indicated.

Urine dipstick and proteinuria interpretation

Dipstick detects protein; confirm persistent proteinuria with spot urine protein-to-creatinine ratio; nephrotic range typically >2 mg/mg.

Steroids in nephrotic syndrome

Corticosteroids are cornerstone therapy for many pediatric nephrotic syndromes, especially MCD; response guides further treatment.

ACE inhibitors/ARBs in proteinuric kidney disease

Used to reduce proteinuria and protect renal function in diabetic and non-diabetic proteinuric CKD.

Polycystic kidney diseases (PKD) in kids

ARPKD presents in infancy with Potter facies and hepatic fibrosis; ADPKD presents later often with hypertension and adult-type renal cysts.