Kidney: Study notes- Super High-yield

Big-picture functions

• Regulation: water, electrolytes, acid–base, blood pressure (via RAAS).

• Excretion: urea, creatinine, drugs/toxins.

• Secretion: active transport of wastes into tubular fluid.

• Gluconeogenesis: kidney supplies glucose during fasting.

Flow of blood → filtrate → urine (terms)

• Blood → plasma → filtration → tubular fluid → urine.

• Only plasma (water + solutes) should be filtered; cells & plasma proteins normally remain in blood (too large & negatively charged).

• Reabsorption: tubule → blood (returns “good stuff”).

• Secretion: blood → tubule (adds “bad stuff”).

• Excretion: what leaves in urine = filtered − reabsorbed + secreted.

Basic renal hemodynamics & key numbers (typical)

• Cardiac output ≈ 5 L/min; kidneys get ~20–25% → renal blood flow (RBF) ≈ 1.0–1.2 L/min.

• Renal plasma flow (RPF) ≈ RBF × plasma fraction (≈0.55) → ≈ 600–650 mL/min.

• GFR ≈ 125 mL/min (≈180 L/day).

• Filtration fraction (FF) = GFR / RPF ≈ 125 / 625 = 0.20 = 20%.

  • Example (simple numbers): if afferent plasma = 100 mL, filtered = 20 mL → GFR = 20 mL/min, FF = 20/100 = 20%.

Glomerular filtration barrier (3 layers)

1. Fenestrated endothelium (glomerular capillaries) — allows plasma but not cells.

2. Glomerular basement membrane — negatively charged (repels negatively charged proteins).

3. Podocytes (foot processes + slit diaphragms) — final sieve.
   → Net effect: plasma filters; cells & proteins return in efferent arteriole.

Starling-style forces in glomerular filtration

• Favoring filtration: glomerular capillary hydrostatic pressure ≈ 60 mmHg and Bowman’s oncotic ≈ 0 mmHg (no protein in filtrate).

• Opposing filtration: Bowman’s space hydrostatic ≈ 18 mmHg and glomerular capillary oncotic ≈ 32 mmHg.

• Compute net (digit-by-digit):

  • Opposing total = 18 + 32 = 50 mmHg.

  • Net filtration pressure = 60 − 50 = 10 mmHg (favors filtration).

Nephron anatomy & function (high-yield)

Order: Bowman's capsule → Proximal convoluted tubule (PCT) → Loop of Henle (descending → thin ascending → thick ascending) → Distal convoluted tubule (DCT) → Collecting duct → minor calyx → major calyx → renal pelvis → ureter.

Proximal convoluted tubule (PCT)

• Main jobs: bulk reabsorption (Na⁺, water, glucose, amino acids, bicarbonate) + secretion (organic acids/bases: uric acid, bile salts, drugs).

• Transport principles:

  • Basolateral Na⁺/K⁺-ATPase (primary active) pumps Na⁺ out → creates low intracellular Na⁺.

  • Apical: Na⁺ flows downhill into cell and cotransports solutes (secondary active).

  • SGLT2 (sodium–glucose cotransporter 2) on apical side reabsorbs glucose + Na⁺ (mnemonic: SGLT2 = in kidney → “2 kidneys”).

  • Basolateral glucose exit: facilitated diffusion (carrier, no ATP).

• Acid–base: carbonic anhydrase inside cells converts CO₂ + H₂O ⇄ H₂CO₃ ⇄ HCO₃⁻ + H⁺. H⁺ secreted via Na⁺/H⁺ exchanger (NHE); HCO₃⁻ reabsorbed.

Loop of Henle — countercurrent multiplier

• Descending limb: thin, permeable to water, impermeable to NaCl → tubular fluid concentrates (osmolality rises up to ~1200 mOsm in inner medulla).

• Ascending limb (thin → thick): impermeable to water, actively reabsorbs NaCl.

  • Thick ascending limb (TAL): NKCC2 = Na⁺/K⁺/2Cl⁻ cotransporter at luminal membrane (reabsorbs Na⁺, K⁺, Cl⁻).

  • TAL also drives reabsorption of Ca²⁺ & Mg²⁺ (paracellular) and is diluting segment.

• Countercurrent setup produces corticomedullary gradient → ability to concentrate urine.

Distal convoluted tubule (DCT) & Collecting ducts

• Early DCT: Na⁺/Cl⁻ cotransporter (NCC) — thiazide diuretic target; PTH acts to increase Ca²⁺ reabsorption here.

• Late DCT & collecting duct cell types:

  • Principal cells: reabsorb Na⁺, secrete K⁺; respond to aldosterone (↑ENaC, ↑Na⁺ reabsorption) and ADH (vasopressin V2 receptors) (↑aquaporin insertion → ↑water reabsorption = free water).

  • α-intercalated cells: acid–base: secrete H⁺ (via H⁺-ATPase/H⁺-K⁺-ATPase) and reabsorb HCO₃⁻ (protect against acidosis).

• Ammonium handling: NH₃ binds H⁺ → NH₄⁺ excreted (one major method for acid elimination). Also titratable acids (H⁺ buffered by phosphate) are used.

Membrane transport & routes (quick)

• Transcellular: through cells (can be active or passive).

• Paracellular: between cells (usually passive).

• Primary active: uses ATP directly (e.g., Na⁺/K⁺-ATPase).

• Secondary active: uses gradient established by primary active (e.g., SGLT2).

• Facilitated diffusion: carrier-mediated, no ATP (e.g., basolateral glucose exit).

Clinical & pharmacologic pearls

• Diuretic targets:

  • Loop diuretics → inhibit NKCC2 (TAL) → block urine concentration ability.

  • Thiazides → inhibit NCC (early DCT).

  • K⁺-sparing (amiloride, spironolactone) → act at principal cell ENaC or aldosterone receptor.

• SGLT2 inhibitors → block PCT glucose reabsorption → glucosuria (used in diabetes).

• Carbonic anhydrase inhibitors (acetazolamide) → act on PCT → reduce HCO₃⁻ reabsorption (can cause metabolic acidosis).

High-yield formulas & concepts (one-liners)

• Urine Excretion = Filtration − Reabsorption + Secretion.

• FF ≈ 20% (GFR ≈125 mL/min; RPF ≈600–650 mL/min).

• Descending = water out (concentrates). Ascending = salt out (dilutes).

• Aldosterone = “salt saver, K⁺ & H⁺ waster.”

• ADH (V2) = free water reabsorption via aquaporins.

Quick study mnemonics

• SGLT2 = “2 kidneys” → kidney SGLT.

• NKCC2 = “Na K 2 Cl” (TAL transporter — loop diuretic target).

• Principals: Aldosterone ↑Na⁺ reabsorption, ↑K⁺ & H⁺ secretion.

• α-intercalated: Acid secretors (H⁺ out) and HCO₃⁻ reabsorption.