GFR and Glomerular Filtration
Normal GFR: approximately 120 mL/min (180 L/day filtered; about 1.5 L/day excreted). Governed by Starling forces across the glomerular capillary.
| Factor | Effect on GFR | Clinical Example |
|---|---|---|
| Afferent arteriole dilation | Increases GFR | Prostaglandins, ANP |
| Afferent arteriole constriction | Decreases GFR | NSAIDs, severe hypotension |
| Efferent arteriole constriction | Increases GFR (initially) | Angiotensin II |
| Efferent arteriole dilation | Decreases GFR | ACE inhibitors and ARBs |
⭐ ACE Inhibitors and KidneyACEi/ARBs dilate EFFERENT arteriole → decrease GFR → expected creatinine rise (up to 30% acceptable). Avoid in bilateral renal artery stenosis — both kidneys depend on Ang II to maintain GFR.
Tubular Reabsorption and Diuretics
| Segment | What is Reabsorbed | Diuretic Target |
|---|---|---|
| Proximal tubule | 67% Na+, water, HCO3-, glucose, amino acids, phosphate, uric acid | Carbonic anhydrase inhibitors (acetazolamide) |
| Loop of Henle (thick ascending) | Na+/K+/2Cl- (25% of Na+); impermeable to water | Loop diuretics (furosemide) — NKCC2 cotransporter |
| Distal convoluted tubule | Na+/Cl- (5-8%); Ca2+ (PTH-stimulated) | Thiazides (NCC cotransporter) |
| Collecting duct | Na+ (aldosterone); water (ADH/vasopressin) | K+-sparing diuretics (spironolactone, amiloride) |
🧐 Diuretics by LocationProximal=Acetazolamide. Loop=Furosemide (NKCC2). DCT=Thiazides (NCC). Collecting Duct=Spironolactone (aldosterone antagonist). Furosemide is most potent — acts on thick ascending limb where 25% of Na+ reabsorption occurs.
Renin-Angiotensin-Aldosterone System
Renin (JGA) → cleaves angiotensinogen to Ang I → ACE (lungs) converts to Ang II → aldosterone (adrenal cortex) + vasoconstriction + ADH release + thirst.
🩹 Aldosterone EffectsCollecting duct: inserts ENaC channels and Na+/K+-ATPase → Na+ reabsorption, K+ and H+ secretion. Net: Na+ and water retention + hypokalemia + metabolic alkalosis. Primary hyperaldosteronism (Conn's): HTN + hypokalemia + metabolic alkalosis.
Acid-Base Physiology
| Disorder | pH | Primary Change | Compensation |
|---|---|---|---|
| Metabolic acidosis | Less than 7.35 | HCO3- decreased | Hyperventilation (Winter's formula: expected PaCO2 = 1.5 x HCO3 + 8 +/- 2) |
| Metabolic alkalosis | Greater than 7.45 | HCO3- increased | Hypoventilation (raise PaCO2) |
| Respiratory acidosis | Less than 7.35 | PaCO2 increased | Kidneys retain HCO3- (days) |
| Respiratory alkalosis | Greater than 7.45 | PaCO2 decreased | Kidneys excrete HCO3- |
🧐 High Anion Gap Metabolic Acidosis — MUDPILESMethanol, Uremia, DKA/starvation ketosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
Key Electrolytes
| Electrolyte | Normal | Hyperstate Signs | Hypostate Signs |
|---|---|---|---|
| Sodium | 135-145 mEq/L | Hypernatremia: thirst, confusion, seizure | Hyponatremia: headache, nausea, seizure (severe) |
| Potassium | 3.5-5.0 mEq/L | Peaked T, wide QRS, fatal arrhythmia | Flat T waves, U waves, weakness, cramps |
| Calcium | 8.5-10.5 mg/dL | Bones stones groans moans; shortened QT | Chvostek/Trousseau; prolonged QT; tetany |
| Magnesium | 1.5-2.5 mEq/L | Loss of DTRs, respiratory depression | Refractory hypokalemia; torsades de pointes |
Renal Hormones
- Erythropoietin (EPO) — peritubular fibroblasts; stimulates RBC production; deficient in CKD → normocytic anemia
- Renin — JGA cells; triggers RAAS; released by decreased renal perfusion, low Na+ delivery, or sympathetic stimulation
- 1,25-dihydroxyvitamin D (calcitriol) — 1-alpha-hydroxylase in kidney converts 25-OH-D3 to active form; promotes Ca2+ and PO4 absorption; deficient in CKD → renal osteodystrophy
- Prostaglandins (PGE2, PGI2) — dilate afferent arteriole to maintain GFR when BP falls; NSAIDs block → AKI in dehydration/low-flow states
Clinical Pearls
⭐ ADH and SIADH vs DIADH (vasopressin): released with high serum osmolarity or low blood volume → V2 receptors in collecting duct → aquaporin-2 insertion → water reabsorption. SIADH: excess ADH → hyponatremia + euvolemia + urine osmolarity greater than 100. Central DI: no ADH → dilute urine + hypernatremia + treats with desmopressin (DDAVP). Nephrogenic DI: ADH present but receptor insensitive → treats with low-Na diet + thiazides.
🩹 FENa InterpretationFENa = (urine Na x plasma Cr) / (plasma Na x urine Cr) x 100. Less than 1% = prerenal. Greater than 2% = intrinsic renal (ATN). Unreliable on diuretics — use FEUrea instead (less than 35% = prerenal).