Memory tricks for renal physiology

Net filtration pressure (NFP) determines GFR. Glomerular hydrostatic pressure (GHP, ~55 mmHg) promotes filtration — blood pressure in the glomerulus. Colloid osmotic pressure (COP, ~30 mmHg) opposes filtration — plasma proteins draw water back. Capsule pressure (CP, ~15 mmHg) opposes filtration — fluid already in Bowman's capsule. NFP = 55 − (30 + 15) = 10 mmHg. Anything increasing GHP increases GFR. Anything increasing COP or CP decreases GFR. Autoregulation keeps GFR stable from BP 80–180 mmHg.

The PCT reabsorbs approximately 65–70% of filtered water, sodium, potassium, and bicarbonate. ALL filtered glucose and amino acids are normally reabsorbed here via secondary active transport (sodium-glucose cotransporter, SGLT2). Glucose threshold: when plasma glucose exceeds ~180 mg/dL, SGLT2 transporters become saturated → glucose spills into urine (glucosuria). SGLT2 inhibitors (flozins) are diabetes drugs that intentionally block SGLT2 → glucose lost in urine → lower blood glucose. PCT is also where many drugs are secreted into the tubule.

The loop of Henle creates a high-osmolarity gradient in the medulla — essential for urine concentration. Descending limb: permeable to water, impermeable to solutes → water leaves by osmosis → filtrate becomes more concentrated. Ascending limb (thick): impermeable to water, actively pumps Na+/K+/Cl- OUT → filtrate becomes dilute, medulla becomes concentrated. The concentrated medullary interstitium then pulls water out of the collecting duct when ADH is present → concentrated urine produced. Loop diuretics (furosemide) block the Na+/K+/2Cl- pump in the thick ascending limb → destroy the gradient → cannot concentrate urine.

Aldosterone is released from the adrenal cortex when angiotensin II rises (low BP) or K+ rises. It binds mineralocorticoid receptors in DCT and collecting duct principal cells → increases Na+ channels (ENaC) on luminal side → Na+ reabsorbed → water follows → BP rises. Simultaneously increases K+ secretion (K+ exits into tubule → excreted) and H+ secretion. Conn's syndrome (primary hyperaldosteronism): excess aldosterone → hypertension + hypokalemia + metabolic alkalosis. Spironolactone is an aldosterone antagonist used as a potassium-sparing diuretic.

Low blood pressure or low Na+ → juxtaglomerular cells release Renin → Renin cleaves angiotensinogen (liver) → Angiotensin I → ACE (lung) converts to Angiotensin II → Angiotensin II: vasoconstriction (raises BP directly), stimulates aldosterone (Na+/water retention), stimulates ADH, stimulates thirst. ACE inhibitors (lisinopril, enalapril) block conversion → less Ang II → less vasoconstriction + less aldosterone → lower BP. ARBs block Ang II receptors. Both are first-line for hypertension and heart failure.

K+ is the most dangerous electrolyte because even small changes cause cardiac arrhythmias. 98% of K+ is intracellular. Factors driving K+ INTO cells: insulin (Na+/K+ ATPase), alkalosis (H+ leaves cells, K+ enters), beta-2 agonists. Factors driving K+ OUT of cells: acidosis (H+ enters cells, K+ leaves), cell lysis, hypertonicity. ECG changes with hyperkalemia: peaked T waves → wide QRS → sine wave → ventricular fibrillation. Treatment of hyperkalemia: calcium gluconate (stabilizes membrane), insulin + glucose (shifts K+ in), sodium bicarbonate (alkalosis shifts K+ in), Kayexalate or dialysis (removes K+).

Sodium is the primary determinant of extracellular fluid volume — where Na+ goes, water follows. The body regulates Na+ to regulate blood volume, not to regulate osmolarity directly (that's regulated separately by ADH). Hyponatremia (Na+ <135): excess water relative to Na+ — causes cerebral edema → confusion, seizures. Hypernatremia (Na+ >145): water deficit relative to Na+ — causes cell shrinkage → thirst, dehydration. ANP (atrial natriuretic peptide) is released when atria stretch → promotes Na+ excretion → lowers BP. Opposes RAAS.

Lungs respond to acid-base in minutes. Kidneys respond in hours to days but have greater capacity. Kidneys regulate pH by: secreting H+ into the tubule (excretes acid), regenerating HCO3- (returns to blood as base), and excreting ammonium (NH4+) — the main way kidneys excrete acid. In metabolic acidosis: kidneys increase H+ secretion and HCO3- reabsorption, increase ammoniagenesis. Renal tubular acidosis (RTA): kidneys fail to excrete H+ → hyperchloremic metabolic acidosis with normal anion gap. Type 1 (distal) most common — cannot acidify urine below pH 5.5.

Loop diuretics (furosemide): block NKCC2 in thick ascending limb — most powerful. Waste Na+, K+, Cl-, Ca2+, Mg2+. Thiazides (hydrochlorothiazide): block NaCl transporter in DCT. Waste Na+, K+, Mg2+. Retain Ca2+ (used in hypercalciuria/kidney stones). Spironolactone: aldosterone antagonist in DCT/CD. Potassium-sparing. Used in heart failure, Conn's. ACE inhibitors: reduce angiotensin II → reduce aldosterone → mild diuresis + K+ retention. Potassium-sparing diuretics also include amiloride (blocks ENaC) and triamterene.

GFR (glomerular filtration rate) = ~125 mL/min = 180 L/day. Of this, ~99% reabsorbed in tubules → only ~1.5L urine/day. GFR regulated by afferent/efferent arteriole tone (controlled by angiotensin II, prostaglandins, ANS). Creatinine clearance used clinically to estimate GFR.

Low BP/Na → kidney JGA releases renin → cleaves angiotensinogen to Ang I → ACE converts to Ang II (lungs) → Ang II: vasoconstriction + stimulates aldosterone from adrenal cortex → aldosterone: Na+ reabsorption in collecting duct → ↑ water retention → ↑ BP.

Respiratory: pH and CO2 move in OPPOSITE directions (↑CO2 → ↓pH = respiratory acidosis). Metabolic: pH and HCO3 move in EQUAL/same direction (↓HCO3 → ↓pH = metabolic acidosis). Kidneys compensate for respiratory disorders; lungs compensate for metabolic disorders.

High plasma osmolality → hypothalamus releases ADH → aquaporin-2 channels inserted into collecting duct → water reabsorption → concentrated urine. Low osmolality or high volume → ADH suppressed → dilute urine. Diabetes insipidus: ADH absent → massive dilute urine output.