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.
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.
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.
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.
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.
The glomerulus filters 180L/day but the body reabsorbs 99% — only 1.5L excreted
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.
The renin-angiotensin-aldosterone system raises BP by retaining sodium and water
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.
Use ROME to determine if compensation is respiratory or metabolic on ABG questions
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.