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The nephron, appearance and concentration

16 min

  • 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

Read the full reference

Try first

Try first

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

The next section explains it.

The next section explains it.

Right. The next section explains why.

The next section explains it.

Get the idea

Each finding traces to a 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 points to the segment that failed:2

SegmentIts jobWhen it fails, urine shows
GlomerulusFilters water and small solutes, keeps cells and most protein backAlbumin, dysmorphic red cells, red cell casts
Proximal tubuleReclaims 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 that point to 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 are confirmed by other tests

Red urine can come from red cells, free hemoglobin, myoglobin, porphyrins, beets or rifampin. The blood pad and microscopy decide which. A negative blood pad with no red cells turns the search 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

Three ways to measure concentration

  • Refractometry reads refractive index, which rises with the number and the mass of dissolved particles. Glucose, protein and contrast media can push it high.
  • The strip pad estimates ionic strength. Uncharged solutes such as glucose, urea and contrast barely register.
  • Osmolality counts dissolved particles per kilogram of water, whatever their mass.3

A gap between refractometer and strip usually means large or uncharged solutes are present. Osmolality measures particle concentration without the mass effect.3

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

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

Why do the two specific gravities disagree?

TestResultPreviousReference intervalFlag
Specific gravity, refractometer1.0381.003–1.035High
Specific gravity, strip1.0151.003–1.035
Glucose, strip≥1,000 mg/dLNegativeHigh
Protein, stripNegativeNegative

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 answer different questions, so the size of the gap is the first thing to see.

  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 has to rule it out.

  4. Explain the gap: the heavy glucose load adds mass that the refractometer reads and the strip does not.

    Glucose carries no charge, so the ionic-strength pad misses it. Its mass raises the refractive index.

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

    Osmolality counts glucose molecules as particles without weighting them by mass.

The gap comes from glucose. Both specific gravities are valid for their methods, and osmolality gives the particle concentration when it is needed.

Your turn

Problem 1 of 3

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 points to 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 load is ordinary.
  2. Ask which segment normally reclaims glucose, amino acids and phosphate.

Review From nephron to urine

Problem 2 of 3

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. Color cannot support that report.

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 points away from RBCs, hemoglobin, and myoglobin, so the evaluation turns to 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, ask what else can color urine red.

Review Color

Problem 3 of 3

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 gap?

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

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 gap as an error hides a real effect 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

  • A urine from Leona Fairweather, 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 look 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 has to stay untreated.

Warming dissolves urates. Phosphates stay, so warming cannot support this identification.

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

Review Color

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 points to infection, so there is no reason to wait for a culture.

Review Color

The clue that settled this case is the alkaline pH with a microscope full of amorphous granules and no cells or bacteria. The cloudiness matched the sediment, and the acid test on a separate aliquot supported phosphates.

Keep

Sources checked