System 04 / Renal transport and acid-base Status: regulation online
Core operating model
The kidney is a regulated transport organ.
It filters broadly, then reabsorbs, secretes and hormonally fine-tunes until urine matches the body's volume, osmolality, electrolyte and acid-base needs.
Master balance equation
Excretion = Filtration - Reabsorption + Secretion
Every nephron question asks what was filtered, reclaimed, secreted or finally lost.
Nephron decision chain
01 / INPUT
Glomerulus
Filters water and small solutes.
02 / BULK
PCT
Reclaims bulk solute and HCO3-.
03 / GRADIENT
Loop
Builds the medullary gradient.
04 / TRIM
DCT
Fine-tunes NaCl and Ca2+.
05 / OUTPUT
Collecting duct
Final water, K+ and acid decisions.
125
mL/min GFR
180
L/day filtrate
65%
PCT Na+/water
8-12
Normal anion gap
01
Segment map
Location predicts transport mechanism.
FILTER / GLOMERULUS
Selective filtration
Fenestrated endothelium, GBM and podocytes filter water and small solutes while excluding cells and albumin.
RECLAIM / PCT
Bulk recovery
Iso-osmotic reabsorption of Na+, water, glucose, amino acids, phosphate and most filtered HCO3-.
MULTIPLY / LOOP
Build the gradient
Descending limb loses water; thick ascending limb reabsorbs salt without water.
CALIBRATE / DCT
Salt and calcium
NCC fine-tunes NaCl; PTH increases Ca2+ reabsorption.
OUTPUT / PRINCIPAL
Na+, K+ and water
ENaC, ROMK and AQP2 respond to aldosterone and ADH.
PH / INTERCALATED
Acid-base control
Alpha cells secrete H+; beta cells secrete HCO3-.
02
Filtration and transporter board
Pressure controls entry; transporters control recovery.
Filtration pressure
Net filtration pressure = PGC - PBS - πGC
Afferent constriction lowers renal blood flow, PGC and GFR.
Efferent constriction lowers renal blood flow but can initially raise PGC and GFR.
NSAIDs remove prostaglandin afferent support. ACEi/ARBs dilate the efferent arteriole.
Transporter + diuretic board
PCT
CA, NHE, SGLT2/SGLT1. Acetazolamide decreases HCO3- reabsorption and causes metabolic acidosis.
TAL
NKCC2. Loop diuretics increase Ca2+ and Mg2+ excretion.
DCT
NCC. Thiazides block NCC and increase Ca2+ reabsorption.
Collecting duct
ENaC / aldosterone. K-sparing drugs reduce K+ loss.
03
Hormonal control
Three signals change the final urine.
Aldosterone
Na+ in, K+/H+ out
Increases ENaC, Na+/K+ ATPase, K+ secretion and H+ secretion. Excess: hypertension, hypokalemia, metabolic alkalosis. Deficiency: hyperkalemia, metabolic acidosis.
ADH
Water permeability
V2 receptors insert AQP2 in principal cells. Central DI responds to desmopressin; nephrogenic DI does not. SIADH causes dilutional hyponatremia.
PTH
Calcium rescue
Increases Ca2+ reabsorption in the DCT. Loop diuretics waste Ca2+; thiazides retain Ca2+.
04
Acid-base operating system
Kidneys control bicarbonate; lungs control carbon dioxide.
Henderson-Hasselbalch equation
pH = 6.1 + log( HCO3- / (0.03 x PaCO2) )
HCO3-
Metabolic component controlled mainly by the kidneys.
PaCO2
Respiratory component controlled mainly by alveolar ventilation.
PCT bicarbonate reclamation
H+ + HCO3-
H2CO3
CO2 + H2O
CO2 enters cell
HCO3- reforms
HCO3- to blood
Filtered HCO3- is reabsorbed indirectly. Carbonic anhydrase enables the CO2 shuttle.
This reclaims but does not make new HCO3-. Acetazolamide causes bicarbonaturia and metabolic acidosis.
05
Primary disorders
Find the primary variable, then predict compensation.
Metabolic acidosis
Primary low HCO3-. Compensation: hyperventilation lowers PaCO2.
Metabolic alkalosis
Primary high HCO3-. Compensation: hypoventilation, limited by oxygenation.
Respiratory acidosis
Primary high PaCO2. Chronic kidney response: retain HCO3- and excrete acid.
Respiratory alkalosis
Primary low PaCO2. Chronic kidney response: excrete more HCO3-.
06
Anion gap and RTA
Separate unmeasured acids from bicarbonate loss.
Anion gap logic
AG = Na+ - (Cl- + HCO3-)
High AG metabolic acidosis: lactate, ketoacids, renal failure, methanol, ethylene glycol and salicylates.
Normal AG metabolic acidosis: diarrhea, RTA, acetazolamide and ureteral diversion.
Renal tubular acidosis
Type 1 distal: impaired alpha-cell H+ secretion, high urine pH, stones, hypokalemia.
Type 2 proximal: impaired PCT HCO3- reabsorption, bicarbonaturia, hypokalemia.
Type 4: hypoaldosteronism or resistance, reduced K+/H+ secretion, hyperkalemia, diabetic nephropathy.
07
New bicarbonate generation
Excreted acid adds new HCO3- to blood.
Titratable acid
Filtered phosphate buffers secreted H+ in urine; each excreted H+ adds new HCO3- to blood.
NH3 traps acid
Glutamine metabolism produces NH4+ and HCO3-. NH3 + H+ → NH4+ trapped in lumen.
Chronic acidosis
Ammonium excretion removes acid without requiring an impossible urine pH.
08
Diuretic effect map
Segment blockade predicts electrolytes and pH.
Acetazolamide
PCT carbonic anhydrase inhibitor → HCO3- loss → metabolic acidosis.
Loop diuretics
TAL NKCC2 block → NaCl, water, Ca2+, Mg2+ loss → hypokalemic metabolic alkalosis.
Thiazides
DCT NCC block → NaCl loss, Ca2+ retention → hypokalemic metabolic alkalosis.
K-sparing
Aldosterone receptor or ENaC block → less K+/H+ secretion → hyperkalemic metabolic acidosis risk.
09
Potassium and water disorders
Electrolytes expose the hidden control failure.
Potassium links acid-base
Hypokalemia promotes H+ secretion and HCO3- reabsorption, helping maintain metabolic alkalosis.
Hyperkalemia reduces ammonium production and contributes to metabolic acidosis, especially type 4 RTA.
Water disorders
Central DI: low ADH, dilute polyuria, improves with desmopressin.
Nephrogenic DI: kidney ADH resistance, little desmopressin response.
SIADH: water retention, low serum osmolality, concentrated urine, dilutional hyponatremia.
Final protocol / nephron
For nephron questions
Identify the segment, transporter, hormone and direction of Na+, water, K+, H+ or HCO3- movement.
Final protocol / acid-base
For acid-base questions
Find the primary change, predict compensation, calculate the anion gap, then connect the pattern to lung, kidney or GI physiology.