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Explanation of Guyton's Figure 29-8: Tubular Fluid Osmolarity Through the Nephron

This graph shows how osmolarity (mOsm/L) changes as fluid travels through each segment of the nephron, under two conditions:

Upper (red) curve = with high levels of ADH (antidiuretic hormone) → concentrated urine
Lower (red) curve = in the absence of ADH → dilute urine

The shaded yellow area between the two curves represents the range of possible outcomes depending on ADH status.

The numbers on the graph are volumes in mL/min flowing at each point.

Segment-by-Segment Walk-Through

1. Proximal Tubule (starts at ~300 mOsm/L, volume = 125 mL/min)

Fluid entering the proximal tubule is isotonic - same osmolarity as plasma: ~300 mOsm/L
About 65% of filtered water and solutes are reabsorbed here, proportionally - so osmolarity stays at 300 mOsm/L throughout
Volume drops from 125 mL/min to ~44 mL/min by the end
The proximal tubule is freely permeable to water, so water follows solutes - osmolarity doesn't change despite massive reabsorption

2. Loop of Henle - Descending Limb (osmolarity rises to ~1200 mOsm/L)

As fluid descends into the medulla, the surrounding interstitium becomes progressively more concentrated (built up by the countercurrent multiplier mechanism)
The descending limb is permeable to water but impermeable to NaCl
So water is pulled OUT by osmosis → tubular fluid becomes more and more concentrated
At the tip of the loop (papilla), osmolarity peaks at ~1200 mOsm/L
Volume is now ~25 mL/min

Key concept - the countercurrent multiplier: The thick ascending limb actively pumps NaCl OUT into the medullary interstitium (but is impermeable to water). This NaCl builds up a concentration gradient from cortex (~300) down to papilla (~1200 mOsm/L). The descending limb, flowing in the opposite direction, equilibrates with this gradient by losing water. The two limbs work together to "multiply" the concentration gradient. - Guyton and Hall, p. 375

3. Loop of Henle - Ascending Limb (osmolarity falls to ~100 mOsm/L)

The thick ascending limb actively transports NaCl, K⁺, Cl⁻ OUT into the interstitium
It is impermeable to water - water cannot follow
So the fluid becomes progressively MORE dilute as it ascends
By the time it exits into the distal tubule, osmolarity has dropped to ~100-140 mOsm/L
This is why the ascending limb is called the "diluting segment" (labeled on the graph)
Volume is ~25 mL/min here

4. Early Distal Tubule / Diluting Segment (~100 mOsm/L)

Behaves just like the thick ascending limb
Continues to reabsorb NaCl while remaining impermeable to water
Fluid stays dilute: ~100 mOsm/L, regardless of ADH
This is the segment labeled "Diluting segment" on the graph

Critical teaching point: Fluid leaving the ascending loop and early distal tubule is always dilute (~100 mOsm/L), regardless of ADH levels. ADH has no effect here. - Guyton and Hall, p. 376

5. Late Distal Tubule + Cortical Collecting Tubule - THE FORK IN THE ROAD

This is where the two curves diverge based on ADH:

With HIGH ADH:

The late distal tubule and cortical collecting tubule become highly permeable to water
Water is reabsorbed back into the cortical interstitium (and carried away by peritubular capillaries)
Osmolarity rises back up toward ~300 mOsm/L
Volume drops from ~25 mL/min to ~8 mL/min (entering collecting duct)

Without ADH:

These segments remain impermeable to water
NaCl continues to be reabsorbed, but water stays in the tubule
Osmolarity drops even further - as low as 50 mOsm/L
Volume stays large (20 mL/min of dilute urine is excreted)

6. Medullary Collecting Duct - Final Concentration

With HIGH ADH:

The medullary collecting duct is highly permeable to water
Fluid equilibrates with the surrounding hyperosmotic medullary interstitium
Osmolarity reaches 1200 mOsm/L - matching the papillary interstitium
Volume shrinks to just 0.2 mL/min of concentrated urine
Urea is also reabsorbed here via special transporters (UTA-1, UTA-3), adding further to medullary hyperosmolarity

Without ADH:

Water is not reabsorbed
~20 mL/min of dilute, large-volume urine is produced

What the Two Curves Tell You at a Glance

Segment	ADH Present	No ADH
Proximal tubule	300 mOsm/L	300 mOsm/L
Descending loop	rises to 1200	rises to 1200
Ascending loop	falls to 100	falls to 100
Late distal/collecting	rises (water reabsorbed)	stays low/falls further
Final urine	~1200 mOsm/L, 0.2 mL/min	~50 mOsm/L, 20 mL/min

The Supporting Mechanism (Why This Works)

This diagram from Guyton (Figure 29-5) shows the whole system:

Diagram of concentrated urine formation showing NaCl, H₂O, and Urea movements across nephron segments with osmolarity values

The entire system depends on three things working together:

Countercurrent multiplier (loop of Henle) - builds the medullary gradient up to 1200 mOsm/L
ADH (vasopressin) - makes the collecting duct water-permeable so fluid can equilibrate with that gradient
Urea recycling - urea from the inner medullary collecting duct diffuses into the interstitium and contributes ~40-50% of the total medullary osmolarity

Without the medullary gradient, ADH would have nothing to equilibrate against. Without ADH, the gradient exists but the collecting duct cannot use it. Both are required to produce concentrated urine. - Guyton and Hall Textbook of Medical Physiology, pp. 372-378

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