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The nephron, appearance and concentration

16 min

Skills you'll build3 skills
  • Match a nephron segment to its role in filtration, reabsorption, or secretion
  • Confirm a urine color or clarity finding with the reagent strip and microscopy
  • Explain a discrepancy between refractometric and strip specific gravity

At the bench: Reconcile urine appearance, chemistry, and microscopy findings

Try first

Try first

A urinalysis shows protein 3+, dysmorphic red cells and red cell casts. Which part of the nephron do these findings indicate?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Urine findings by nephron segment

The glomerulus filters plasma. The tubules return water and solutes to the blood and add selected substances to the urine.1,2 A urine finding indicates the segment involved:2

SegmentFunctionUrine findings when it fails
GlomerulusFilters water and small solutes, retains cells and most proteinAlbumin, dysmorphic red cells, red cell casts
Proximal tubuleReabsorbs most water and sodium, and glucose, amino acids, phosphate and bicarbonateGlucose with a normal blood glucose, amino acids, phosphate, small proteins
Loop of HenleBuilds the medullary concentration gradientDilute urine when water should be conserved
Distal tubule and collecting ductAdjusts water, sodium, potassium and acid under hormonal controlAbnormal concentration or acidification

Findings from the same segment support each other. A finding that fits no segment is a reason to recheck the specimen or the method.

Color and clarity

Red urine can come from red cells, free hemoglobin, myoglobin, porphyrins, beets or rifampin. The blood pad and microscopy distinguish them. A negative blood pad with no red cells points to nonheme pigments and drugs.3

Cloudy urine can be harmless. Amorphous phosphates form a white haze in alkaline urine, and amorphous urates form a pink one in cold, acidic urine. Cells, bacteria and yeast cloud urine too. Warming dissolves urates. Dilute acid dissolves phosphates in a separate aliquot tested under a validated procedure. The clarity grade should match the amount of sediment. A mismatch calls for a check of mixing, technique and specimen identity.3

Measuring urine concentration

  • Refractometry measures refractive index, which increases with the number and the mass of dissolved particles. Glucose, protein and contrast media can raise it.
  • The strip pad estimates ionic strength. Uncharged solutes such as glucose, urea and contrast have little effect.
  • Osmolality measures dissolved particles per kilogram of water, regardless of their mass.3

A difference between the refractometer and the strip usually indicates large or uncharged solutes. Osmolality measures particle concentration without the mass effect.3

Follow the bench demonstration

Sources for this step
References
  1. National Institute of Diabetes and Digestive and Kidney Diseases. Your kidneys and how they work. Accessed September 27, 2026. https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work
  2. Strasinger SK, Di Lorenzo MS. Urinalysis and Body Fluids. 7th ed. F.A. Davis; 2021.
  3. Kouri TT, Hofmann W, Falbo R, et al. The EFLM European urinalysis guideline 2023. Clin Chem Lab Med. 2024;62(9):1653-1786. doi:10.1515/cclm-2024-0070

Watch one

Read each decision and its explanation.

A random urine comes from Ines Blank, 44, admitted with poorly controlled diabetes. She has had no contrast study.

Why do the two specific gravities disagree?

TestResultReference intervalFlag
Specific gravity, refractometer1.038 High1.003–1.0351.003–1.035High
Specific gravity, strip1.0151.003–1.0351.003–1.035
Glucose, strip≥1,000 mg/dL HighNegativeNegativeHigh
Protein, stripNegativeNegativeNegative

Specimen: Not measured on urine. Random urine, fresh, well mixed

  1. Compare the two readings: the refractometer is 0.023 higher than the strip.

    The two methods measure different properties, so the size of the difference is noted first.

  2. Look for such a solute on the strip: glucose is 1,000 mg/dL or more, and protein is negative.

    Large or uncharged solutes raise the refractometer and leave the strip pad nearly unchanged.

  3. Check the history: no contrast study, which leaves glucose as the solute.

    Contrast media give the same pattern, so the history is checked.

  4. Explain the difference: the high glucose adds mass that the refractometer measures and the strip does not.

    Glucose is uncharged, so the ionic-strength pad does not detect it. Its mass raises the refractive index.

  5. When the physician needs her particle concentration, osmolality measures it directly.

    Osmolality counts glucose molecules as particles without regard to mass.

The difference is caused by glucose. Both specific gravities are valid for their methods, and osmolality gives the particle concentration when it is needed.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

Glycosuria with normal blood glucose, aminoaciduria, and phosphate wasting suggest impaired function in which segment?

Incorrect. Glomerular injury lets protein and RBCs into the filtrate. Loss of normally reclaimed small solutes with normal blood glucose indicates a defect in tubular reabsorption.

Correct. The proximal tubule normally reclaims filtered glucose, amino acids, phosphate, and bicarbonate, so its dysfunction lets them escape into urine.

Incorrect. The collecting duct adjusts water and electrolyte excretion. Glucose, amino acids, and phosphate are reclaimed earlier, in the proximal tubule.

Hint
  1. Blood glucose is normal, so the filtered glucose load is normal.
  2. Consider which segment reabsorbs glucose, amino acids and phosphate.

Review From nephron to urine

Problem 2 of 3 · Hints available

Urine is red, but a valid blood-pad reaction is negative and microscopy finds no RBCs. Which direction of investigation fits?

Incorrect. Hematuria means intact red blood cells (RBCs), and microscopy found none. Urine color does not establish hematuria.

Incorrect. Myoglobin has pseudoperoxidase activity and makes a valid blood pad positive, so a negative pad argues against it.

Correct. A negative blood reaction with no RBCs argues against RBCs, hemoglobin, and myoglobin, so investigate nonheme causes such as porphyrins, beets, or rifampin.

Hint
  1. The blood pad reacts with heme from red cells, hemoglobin and myoglobin.
  2. With the pad negative and no red cells seen, consider what else can color urine red.

Review Color

Problem 3 of 3 · On your own

Two hours after a CT scan with contrast, a urine gives a refractometer specific gravity of 1.050 and a strip specific gravity of 1.005. Glucose and protein pads are negative. What explains the difference?

Contrast molecules are large and uncharged. Their mass raises the refractometer reading, and the ionic-strength pad responds very little.

The two methods measure different properties, and both can be working correctly. A repeat strip gives the same low reading.

Assumed strip and refractometer detect the same solutes

The strip responds to ionic strength. Refractometry responds to solute mass as well as number. Glucose, protein, and contrast media raise a refractometer reading with little strip response. Treating the difference as an error overlooks the real contribution of these nonionic or large solutes.

A dilute urine would lower both readings. The refractometer here reads above the physiologic range.

The protein pad is negative. Contrast from the scan accounts for the high refractometer reading.

Review Measurement principles

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • A urine from Leona Drew, 35, reaches the bench 20 minutes after collection, at room temperature.
  • It is pale yellow and cloudy with a white haze.
  • The strip shows pH 7.5 and negative blood, nitrite and leukocyte esterase. Both specific gravities read 1.015.
  • Microscopy shows many colorless amorphous granules, 0–2 WBC/hpf and no bacteria.
Decision 1 of 3

What best explains the cloudiness?

Urates precipitate in acidic urine and appear pink when cold. This urine is alkaline and fresh.

Phosphates form a white haze in alkaline urine, and the microscope shows abundant amorphous granules with no increase in cells or bacteria.

The esterase and nitrite pads are negative, and microscopy shows few white cells and no bacteria.

Review Color

Decision 2 of 3

How do you support the identification?

Acid changes the pH, alters particles and lyses red cells. The routine specimen stays untreated.

Warming dissolves urates. Phosphates do not dissolve, so warming does not support this identification.

Phosphates dissolve in acid. Using a separate aliquot keeps the routine specimen unchanged for the strip and microscopy.

Review Common crystals

Decision 3 of 3

The acid aliquot clears. What do you do with the urinalysis?

The cloudiness is explained by a harmless precipitate, and every other result agrees with it.

The specimen is fresh and correctly handled. A new one would show the same precipitate.

Nothing in this urinalysis suggests infection, so there is no reason to wait for a culture.

Review Color

The identification rests on the alkaline pH with abundant amorphous granules and no cells or bacteria. The cloudiness matched the sediment, and the acid test on a separate aliquot supported phosphates.

For reference

Sources checked