Biology, and one of the highest-yield single structures on the exam. Most questions reduce to knowing what happens in which segment and what the driving force is.

The Organizational Logic

The kidney does not decide what to keep. It dumps nearly everything into the tubule and then selectively reclaims what it needs. Filtration is indiscriminate; reabsorption is precise.

That is a strange design until you notice the advantage: anything the body has no dedicated transporter for gets excreted by default. Novel toxins and metabolites are eliminated without the body needing to recognize them.

Three processes:

• Filtration — plasma pushed into the tubule at the glomerulus
• Reabsorption — moving substances from tubule back into blood
• Secretion — moving substances from blood into tubule

Excretion = filtration − reabsorption + secretion.

Glomerulus and Bowman's Capsule

Filtration is driven by hydrostatic pressure in the glomerular capillaries, opposed by oncotic pressure from plasma proteins and by hydrostatic pressure in Bowman's space. Net filtration pressure is what remains.

The filtration barrier has three layers: fenestrated endothelium, basement membrane, and podocyte foot processes. It excludes cells and most proteins. Albumin is largely retained both by size and by the negative charge of the basement membrane — which is why loss of that charge in some glomerular diseases produces proteinuria even with intact pore size.

The glomerulus sits between two arterioles, not an arteriole and a venule. This is the key structural fact:

• Constrict the afferent arteriole → less blood in → GFR falls
• Constrict the efferent arteriole → blood backs up → glomerular pressure rises → GFR rises

Angiotensin II preferentially constricts the efferent arteriole, which is how it maintains GFR when perfusion drops.

Proximal Convoluted Tubule

The workhorse. Roughly 65–70% of filtered sodium and water is reabsorbed here, along with essentially 100% of glucose and amino acids under normal conditions.

Reabsorption is isotonic — solute and water leave together, so the fluid entering the loop of Henle has about the same osmolarity as plasma. Volume drops sharply; concentration does not.

The driving force everywhere is the Na⁺/K⁺ ATPase on the basolateral membrane. It pumps sodium out of the cell into the interstitium, keeping intracellular sodium low, which creates the gradient that powers apical secondary active transport. Glucose and amino acids ride in on sodium cotransporters.

Glucose and the transport maximum: glucose reabsorption saturates. Above roughly 180–200 mg/dL plasma glucose, the transporters are overwhelmed and glucose spills into urine. This is glycosuria in diabetes, and it drives osmotic diuresis — glucose in the tubule holds water there, producing the polyuria and polydipsia.

The PCT is also the main site of secretion of organic acids and bases, including many drugs.

Loop of Henle

The countercurrent multiplier. Its job is to establish a concentration gradient in the medullary interstitium, running from ~300 mOsm at the cortex to ~1200 mOsm at the inner medulla.

Descending limb — permeable to water, impermeable to solute. Water leaves as the filtrate descends into increasingly concentrated interstitium. Filtrate becomes concentrated.

Ascending limb — impermeable to water, actively transports solute out via the Na⁺/K⁺/2Cl⁻ cotransporter. Filtrate becomes dilute. This is sometimes called the "diluting segment."

The two limbs working in opposite directions is what multiplies the gradient. The vasa recta run alongside as a countercurrent exchanger, supplying blood to the medulla without washing the gradient away.

Loop diuretics (furosemide) block the Na⁺/K⁺/2Cl⁻ transporter. They are the most powerful diuretics because they destroy the gradient the entire concentrating mechanism depends on.

Distal Convoluted Tubule

Fine-tuning, under hormonal control.

Aldosterone acts here and on the collecting duct: increases Na⁺ reabsorption and K⁺ secretion. Sodium retention brings water with it, raising blood volume and pressure.

PTH increases calcium reabsorption here.

Thiazide diuretics act on the Na⁺/Cl⁻ cotransporter in the DCT.

Collecting Duct

Final water regulation, controlled by ADH (vasopressin).

ADH inserts aquaporin-2 channels into the apical membrane, making the duct permeable to water. Water then flows out into the concentrated medullary interstitium, producing concentrated urine.

• ADH high (dehydration) → aquaporins inserted → water reabsorbed → small volume of concentrated urine
• ADH low (overhydration) → few aquaporins → water stays in tubule → large volume of dilute urine

Note the dependency: ADH only works because the loop of Henle built the medullary gradient. Without the gradient there is nowhere for the water to go.

Diabetes insipidus is failure of this system — either no ADH (central) or no renal response to it (nephrogenic). Both produce copious dilute urine. Unrelated to diabetes mellitus except that both were named for producing large urine volumes.

Hormonal Control

RAAS: low blood pressure or low sodium delivery → juxtaglomerular cells release renin → angiotensinogen to angiotensin I → ACE (in lung) converts to angiotensin II → vasoconstriction, efferent arteriolar constriction, aldosterone release, ADH release, thirst. Net effect: raise blood pressure and volume.

ANP opposes this. Released by atrial stretch when volume is high; promotes sodium and water excretion, dilates the afferent arteriole.

Macula densa cells sense NaCl in the distal tubule and adjust afferent arteriolar tone — tubuloglomerular feedback.

What Gets Tested

• Which segment reabsorbs the most sodium (PCT)
• Effect of afferent vs. efferent constriction on GFR
• Osmolarity at different points along the tubule
• Why glycosuria causes polyuria
• ADH and aquaporin mechanism
• Aldosterone's effect on K⁺ (secreted, not reabsorbed)
• Where a given diuretic acts

A useful check for any nephron question: ask what the osmotic gradient is at that location and what the membrane's permeability is. Water moves only if both a gradient and a channel exist.