Renal physiology for FCPS Part 1
Renal physiology questions test where each substance is handled along the nephron, how GFR is controlled and measured, and how the kidney concentrates urine. Learn the nephron segment by segment.
On this page
The approach that works
Renal physiology feels complicated until you walk along the nephron in order. Almost every question asks one of three things:
- Where along the nephron a substance or drug acts.
- What controls filtration or reabsorption.
- How to calculate clearance or GFR.
Filtration
- GFR is about 125 mL/min (180 L/day). About 20% of renal plasma flow is filtered: that is the filtration fraction.
- Filtration depends on Starling forces: glomerular capillary pressure pushes fluid out; plasma oncotic pressure and Bowman's capsule pressure hold it back.
- Afferent arteriole constriction lowers GFR. Efferent arteriole constriction raises GFR (up to a point) and raises the filtration fraction. This is why ACE inhibitors, which dilate the efferent arteriole, can drop GFR in bilateral renal artery stenosis.
- Autoregulation keeps GFR steady across mean arterial pressures of about 80 to 180 mmHg, through the myogenic response and tubuloglomerular feedback (macula densa).
Clearance
- Clearance = (urine concentration × urine flow) / plasma concentration.
- Inulin clearance equals GFR (freely filtered, not reabsorbed or secreted).
- Creatinine clearance slightly overestimates GFR because a little creatinine is secreted.
- PAH clearance measures effective renal plasma flow (filtered and almost completely secreted).
- Glucose clearance is normally zero, until plasma glucose exceeds the renal threshold (about 10 mmol/L).
Along the nephron
| Segment | What it does | Drug acting there |
|---|---|---|
| Proximal tubule | Reabsorbs about two-thirds of filtered sodium and water, all glucose and amino acids, most bicarbonate; secretes organic acids and drugs | Acetazolamide (carbonic anhydrase), SGLT2 inhibitors |
| Descending limb of loop | Permeable to water, not salt | — |
| Thick ascending limb | Na⁺/K⁺/2Cl⁻ cotransporter; impermeable to water; reabsorbs Ca²⁺ and Mg²⁺ | Loop diuretics (furosemide) |
| Distal convoluted tubule | Na⁺/Cl⁻ cotransporter; PTH-controlled calcium reabsorption | Thiazides |
| Collecting duct (principal cells) | Na⁺ reabsorption through ENaC and K⁺ secretion under aldosterone; water reabsorption through aquaporin-2 under ADH | Spironolactone, amiloride |
| Collecting duct (intercalated cells) | H⁺ secretion, acid–base | — |
Loop diuretics make you lose calcium. Thiazides make you keep it. That one contrast answers many questions about stones, hypercalcaemia and osteoporosis.
Concentrating the urine
- The countercurrent multiplier in the loop of Henle builds a salty medullary interstitium, up to about 1,200 mOsm/kg at the papilla.
- Urea recycling adds to medullary concentration.
- The vasa recta act as countercurrent exchangers, so blood flow does not wash the gradient away.
- ADH inserts aquaporin-2 into the collecting duct, so water leaves into the salty medulla and urine becomes concentrated.
- Without ADH (central diabetes insipidus) or without a response to it (nephrogenic diabetes insipidus, lithium), large volumes of dilute urine follow.
Hormones
| Hormone | Main renal effect |
|---|---|
| ADH | Water reabsorption in the collecting duct |
| Aldosterone | Na⁺ reabsorption, K⁺ and H⁺ secretion |
| Angiotensin II | Efferent constriction, proximal Na⁺ reabsorption, aldosterone release |
| ANP | Natriuresis, afferent dilatation |
| PTH | Increases distal Ca²⁺ reabsorption, decreases phosphate reabsorption, activates vitamin D |
The kidney also makes erythropoietin (peritubular interstitial cells) and calcitriol (1α-hydroxylase in the proximal tubule).
Acid–base handling
- The proximal tubule reclaims most filtered bicarbonate.
- The distal nephron makes new bicarbonate by excreting acid as titratable acid and ammonium.
- Renal compensation for respiratory disorders takes days, unlike respiratory compensation for metabolic disorders, which takes minutes to hours.
Common traps
- The proximal tubule reabsorbs most sodium overall, but the collecting duct is where fine control happens.
- The thick ascending limb is the diluting segment, because it removes salt without water.
- SGLT2 inhibitors act on the proximal tubule and cause glycosuria.
- Hypokalaemia is a side effect of both loop and thiazide diuretics; spironolactone and amiloride cause hyperkalaemia.
How to revise in one week
- Day 1: GFR, its control and autoregulation.
- Day 2: clearance, with calculation practice.
- Day 3: the nephron segment by segment, with the drug for each.
- Day 4: concentration and dilution, ADH and diabetes insipidus.
- Day 5: hormones, calcium and phosphate.
- Days 6 to 7: acid–base handling, then mixed questions.
Practise these in the FCPS-1 Prep question bank. Renal questions link to a full topic review with the nephron drawn segment by segment.
Read next: Acid-base and ABGs · Physiology high-yield · Pharmacology high-yield
Frequently asked questions
Are clearance calculations common?
Yes. Expect at least one question asking you to calculate clearance or identify which substance measures GFR or renal plasma flow.
Do I need to know diuretics in physiology?
Yes. Diuretic questions are really nephron questions, and they appear in both physiology and pharmacology.
What is the single most useful renal fact?
Loop diuretics increase calcium loss and thiazides reduce it. It answers questions across physiology, pharmacology and pathology.