Filtration, reabsorption, secretion, fluid balance, electrolytes — the kidneys regulate virtually every aspect of blood composition. These memory tricks make the physiology of urine formation and fluid balance stick.
What drives glomerular filtration — the three forces in balance
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.
GHP ↑
High BP → more filtration. Afferent dilation or efferent constriction increases GHP.
COP ↑
High plasma proteins → less filtration. Dehydration concentrates proteins → GFR drops.
CP ↑
Ureteral obstruction → backs up → increased capsule pressure → GFR drops.
Autoregulation
Myogenic reflex + tubuloglomerular feedback keep GFR stable 80–180 mmHg.
PCT Reabsorption
PCT reabsorbs ALL glucose · ALL amino acids · 65% Na+ · 65% water
Proximal convoluted tubule — site of most reabsorption
What the PCT reabsorbs — and the glucose threshold rule
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.
100% reabsorbed via specific transporters. Fanconi syndrome = failure here.
Na+ (65%)
Na+/K+ ATPase on basolateral side drives reabsorption. Na+ follows down gradient.
HCO3- (90%)
Reabsorbed in PCT as CO2 (carbonic anhydrase). Important for acid-base.
Loop of Henle Countercurrent
Down = water OUT · Up = salt OUT · Creates medullary gradient
Descending limb: water permeable · Ascending limb: impermeable to water, pumps salt
The countercurrent multiplier — how the kidney concentrates urine
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.
Descending limb
Water permeable — osmosis concentrates filtrate. Thin, no active transport.
300 mOsm at cortex → 1200 mOsm at papilla. Urea contributes 50%.
Furosemide
Blocks NKCC2 → destroys gradient → massive water and salt loss → powerful diuresis.
DCT and Aldosterone
Aldosterone = Na+ IN · K+ OUT · H+ OUT
Aldosterone acts on DCT and collecting duct principal cells
Aldosterone's action on the distal tubule — and the clinical consequences
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.
Na+ reabsorption
Via ENaC channels → water follows → volume expansion → BP increases.
K+ secretion
K+ excreted in exchange for Na+. Hyperaldosteronism → hypokalemia.
H+ secretion
Increased H+ loss → metabolic alkalosis in hyperaldosteronism.
Spironolactone
Aldosterone antagonist → K+ sparing diuretic. Used in heart failure, Conn's.
RAAS System
Low BP → Renin → Angiotensin I → ACE → Angiotensin II → Aldosterone → BP UP
Renin-Angiotensin-Aldosterone System — the blood pressure cascade
The RAAS cascade — the most important blood pressure regulation system
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.
The three electrolytes and their primary physiological roles
Why sodium determines fluid volume — and how the body regulates it
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.
Released by atria when stretched → promotes Na+ excretion → opposes RAAS.
SIADH
Excess ADH → water retention → dilutional hyponatremia. Common in lung cancer.
Renal Acid-Base
Kidneys excrete H+ · Kidneys regenerate HCO3- · Slowest but most powerful buffer
Renal acid-base regulation — slower than lungs but more powerful
How kidneys regulate pH — the long-term acid-base buffer
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.
H+ secretion
PCT and collecting duct. Titratable acid and NH4+ are the main H+ carriers.
HCO3- reabsorption
90% in PCT as CO2. Regenerated in intercalated cells of collecting duct.
Ammoniagenesis
Glutamine → NH3 → NH4+ excreted. Increases dramatically in acidosis.
RTA Type 1
Cannot acidify urine. Urine pH >5.5 even in acidosis. Kidney stones risk.
Diuretic Classes
LAST — Loop · ACE inhibitor · Spironolactone · Thiazide
Four major diuretic classes — site of action determines potency and electrolyte effects
Diuretics — where each acts and what electrolyte it wastes
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.
Loop diuretics
Most potent. Furosemide. Hypokalemia, hyponatremia, hypocalcemia, ototoxicity.