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Human Physiology · Renal system

Tubular Reabsorption and Secretion

Of the 180 litres filtered each day, only one or two leave as urine. The tubules reclaim water, salt, glucose and amino acids, and actively secrete waste, drugs, potassium and acid. This page explains how, where and why it matters for diabetes, heart failure and the drugs your patients take.

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Part 5 · Renal System · Chapter 22 of 47

Learning objectives

By the end of this page you should be able to:

  • Describe what each nephron segment reabsorbs and secretes.
  • Explain how the Na/K ATPase powers tubular transport.
  • Explain the transport maximum, using glucose as the example.
  • Describe potassium handling and the effect of aldosterone.
  • Identify where diuretics act and their side effects relevant to exercise.
  • Describe SGLT2 inhibition and its effect in heart failure.

Why it matters

A large share of older patients take diuretics, and SGLT2 inhibitors are increasingly prescribed for diabetes, heart failure and kidney disease. These drugs act on the tubule, and their effects, such as dehydration, low potassium and dizziness, show up during exercise.

Understanding the tubule also explains why glucose appears in the urine in diabetes and why potassium disorders cause muscle weakness.

Three processes

ProcessDirectionExamples
FiltrationBlood → tubule (glomerulus)Water, salts, glucose, urea
ReabsorptionTubule → bloodMost water and sodium; all glucose and amino acids normally
SecretionBlood → tubulePotassium, hydrogen ions, many drugs, creatinine (small amount)

Amount excreted = amount filtered − amount reabsorbed + amount secreted.

Sodium and water along the nephron

Figure 1 · Where sodium and water are reabsorbed

Percentage of filtered sodium reabsorbed in each nephron segment A bar divided by segment: proximal tubule about 65 per cent, loop of Henle about 25 per cent, distal tubule about 5 per cent, collecting duct about 4 per cent, and under 1 per cent excreted. 65%25%Proximal tubulebulk, iso-osmotic reabsorptionLoop of Henlebuilds medullary gradientDistal tubule about 5%Collecting duct about 4%Excreted under 1%fine-tuned by hormonesShare of filtered sodium reabsorbed along the nephron
The bulk work is early; the fine-tuning is late. Hormones act on the last few per cent, which is enough to change daily excretion greatly. Approximate textbook values.
SegmentMain workHormonal control
Proximal tubuleAbout two thirds of sodium and water; all glucose and amino acids; bicarbonateAngiotensin II increases sodium uptake
Loop of HenleSodium and chloride from the thick ascending limb; water from the descending limbLittle
Distal tubuleSodium and chloride; calciumParathyroid hormone (calcium)
Collecting ductSodium (in exchange for potassium), waterAldosterone (sodium, potassium); antidiuretic hormone (water)

How the proximal tubule works

Figure 2 · Inside a proximal tubule cell

Transporters on the lumen and blood sides of a proximal tubule cell On the lumen side, SGLT2 carries sodium and glucose into the cell together, and a sodium-hydrogen exchanger brings in sodium and sends out hydrogen ions. On the blood side, the sodium-potassium pump pushes three sodium out for two potassium in, and GLUT2 lets glucose leave. Water follows the solutes. Tubule lumenBlood (peritubular capillary)Proximal tubule cellSGLT2Na⁺ + glucoseNHENa⁺ inH⁺ outwater followsNa/KATPase3 Na⁺ out2 K⁺ inGLUT2glucose outlow Na⁺ insidekeeps the gradient
One pump powers everything. The Na/K ATPase keeps cell sodium low, so sodium flows in from the lumen and drags glucose with it. SGLT2 carries about 90% of filtered glucose [1].

On the blood side of every tubule cell, the Na/K ATPase pumps sodium out and keeps sodium inside the cell low. Sodium then flows in from the lumen down its gradient through co-transporters and exchangers, carrying glucose, amino acids and phosphate with it, or swapping for hydrogen ions.

Water follows the solutes through water channels and between cells, so proximal reabsorption is iso-osmotic. This is secondary active transport: the pump spends ATP, and the co-transporters use the resulting gradient.

Transport maximum: the glucose example

DeFronzo and colleagues describe how the kidney normally reabsorbs all filtered glucose. SGLT2, a low-affinity, high-capacity transporter, carries about 90%; SGLT1 carries the rest [1].

Figure 3 · Glucose: a transporter with a ceiling

Glucose filtered, reabsorbed and excreted against plasma glucose Filtered glucose rises in a straight line with plasma glucose. Reabsorbed glucose follows it until it levels off at a maximum of about 375 milligrams per minute. Excreted glucose is zero until plasma glucose passes about 180 to 200 milligrams per decilitre, then rises. renal thresholdabout 180–200 mg/dL01002003004005006000200400600800Plasma glucose (mg/dL)Glucose (mg/min)FilteredReabsorbed(maximum about 375)Excreted
Glucose in the urine means the transporters are saturated. In poorly controlled diabetes SGLT2 activity actually increases, raising the threshold [1]. Typical values at GFR 125 mL/min.

Transporters can only work so fast. When plasma glucose rises above about 180–200 mg/dL, the filtered load exceeds the transport maximum and glucose spills into the urine. Glucose in the urine draws water with it, which is why uncontrolled diabetes causes thirst and frequent urination.

In poorly controlled diabetes, SGLT2 activity increases, so the kidney reabsorbs up to about 20% more glucose and helps keep blood glucose high [1].

Potassium

Almost all filtered potassium is reabsorbed early. Potassium excretion is then set by secretion in the collecting duct, which aldosterone increases. High dietary potassium raises aldosterone and secretion; diuretics that deliver more sodium to the collecting duct increase potassium loss.

DisorderCommon causesEffects on muscle and heart
Low potassium (hypokalaemia)Loop and thiazide diuretics, vomiting, diarrhoeaWeakness, cramps, arrhythmias
High potassium (hyperkalaemia)Kidney failure, potassium-sparing drugs, muscle breakdownWeakness, dangerous arrhythmias

These effects follow from Chapter 5: potassium sets the resting membrane potential. Abnormal potassium makes muscle and heart cells less excitable or unstable.

Secretion of drugs and waste

The proximal tubule has transporters that secrete organic acids and bases, including many drugs such as penicillins and some diuretics. This is why reduced kidney function raises the blood levels of many drugs, and why doses must be adjusted.

Diuretics

Figure 4 · Where diuretics act

Sites of action of the main diuretic groups along the nephron A nephron with four marked sites: SGLT2 inhibitors in the proximal tubule, loop diuretics such as furosemide in the thick ascending limb, thiazides in the distal tubule, and potassium-sparing diuretics such as spironolactone in the collecting duct. SGLT2 inhibitorsproximal tubuleLoop diureticsfurosemide; thick ascending limbThiazidesdistal tubulePotassium-sparingspironolactone; collecting duct
Many of your patients take these. Loop and thiazide diuretics can lower potassium and cause dehydration, cramps and postural dizziness; potassium-sparing drugs can raise potassium.
GroupSite and actionExercise-relevant side effects
Loop (furosemide)Thick ascending limb; block Na-K-2Cl uptakeLarge fluid loss, low potassium, postural dizziness
ThiazideDistal tubule; block Na-Cl uptakeLow potassium and sodium, cramps
Potassium-sparing (spironolactone)Collecting duct; oppose aldosteroneHigh potassium
SGLT2 inhibitorsProximal tubule; block glucose and sodium uptakeMild fluid loss, genital infection; rare ketoacidosis

SGLT2 inhibitors in heart failure

SGLT2 inhibitors were developed for diabetes but turned out to protect the heart. McMurray and colleagues randomised 4,744 patients with heart failure and reduced ejection fraction to dapagliflozin or placebo, on top of usual therapy [2].

Figure 5 · A tubule drug that helps the heart

Outcomes with dapagliflozin versus placebo in heart failure with reduced ejection fraction Paired bars. Worsening heart failure or cardiovascular death occurred in 21.2 per cent with placebo and 16.3 per cent with dapagliflozin; first worsening heart failure in 13.7 and 10.0 per cent; cardiovascular death in 11.5 and 9.6 per cent. 21.2%Placebo16.3%DapagliflozinWorsening HF or CV death13.7%Placebo10.0%DapagliflozinFirst worsening HF event11.5%Placebo9.6%DapagliflozinCardiovascular death
Blocking glucose reabsorption reduced heart failure events, with or without diabetes, over a median of 18.2 months [2].

Worsening heart failure or cardiovascular death fell from 21.2% to 16.3% [2]. Benefits were similar in patients with and without diabetes, and events from volume depletion or kidney dysfunction did not differ between groups [2].

Practical skill · exercising patients on diuretics

Check for postural blood pressure drops before and after exercise. Ask about cramps and weakness, which may signal low potassium. Avoid exercising in heat without fluid planning, and coordinate exercise timing with diuretic doses where possible.

Clinical relevance for the physiotherapist

  • Diabetes. Glucose in the urine causes fluid loss; dehydration lowers exercise tolerance [1].
  • Heart failure. Many patients now take SGLT2 inhibitors; they reduce heart failure events [2].
  • Potassium. Unexplained weakness or cramps in a patient on diuretics may reflect low potassium.
  • Kidney impairment. Drugs cleared by secretion accumulate; side effects may affect balance and alertness.
  • Hydration. Diuretics plus heat plus exercise raise the risk of dehydration and kidney injury.

Assessment and application

SituationLikely mechanismAction
Dizzy on standing after starting furosemideVolume lossPostural BP; graded mobilisation; inform team
Leg cramps and weakness on a thiazidePossible low potassiumReport; blood test may be needed
Thirst and frequent urination in a patient with diabetesGlucose above the renal threshold [1]Check glucose before exercise
Heart failure patient started on dapagliflozinMild diuresis; better outcomes [2]Monitor hydration and BP during exercise

Common mistakes

  • Assuming the collecting duct does most reabsorption; the proximal tubule does.
  • Forgetting that glucose reabsorption has a maximum [1].
  • Thinking SGLT2 inhibitors are only diabetes drugs [2].
  • Ignoring potassium as a cause of weakness.
  • Exercising patients on diuretics in heat without monitoring.

Exam preparation

Long answer

Describe tubular reabsorption, with special reference to sodium and glucose.

  • Segmental handling of sodium (Figure 1).
  • Mechanism in the proximal tubule (Figure 2).
  • Glucose: SGLT2, transport maximum and threshold [1] (Figure 3).
  • Hormonal control: aldosterone, angiotensin II, ADH.
  • Clinical: diuretics and SGLT2 inhibitors [2].

Short notes

  • Transport maximum.
  • Renal threshold for glucose [1].
  • Potassium handling.
  • Diuretics.

Viva and practical

  • “Where is most sodium reabsorbed?” — the proximal tubule.
  • “What is the renal threshold for glucose?” — about 180–200 mg/dL [1].
  • “Name a kidney drug that helps heart failure.” — dapagliflozin [2].
  • OSCE: review medications before exercise testing.

Current evidence

Exam and traditional teaching

Glucose handling is taught only as a transport maximum, and diuretics are grouped by site.

What the evidence adds

The kidney actively contributes to high glucose in diabetes through increased SGLT2 activity [1].

Blocking SGLT2 reduces heart failure events and cardiovascular death, with or without diabetes [2].

What the student should understand

The tubule is a set of pumps and carriers. Drugs that act on them change fluid, potassium and glucose, and you will see those changes during exercise.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. Which transporter reabsorbs about 90% of filtered glucose?
  1. (A) SGLT1
  2. (B) SGLT2
  3. (C) GLUT4
  4. (D) Na/K ATPase

Answer: (B) SGLT2 in the proximal tubule reabsorbs about 90%; SGLT1 the remaining 10% [1].

Q2. SGLT2 is best described as:
  1. (A) High-affinity, low-capacity
  2. (B) Low-affinity, high-capacity
  3. (C) A water channel
  4. (D) A potassium pump

Answer: (B) SGLT2 is low-affinity and high-capacity, while SGLT1 is high-affinity and low-capacity [1].

Q3. In poorly controlled diabetes, renal glucose reabsorption may:
  1. (A) Fall to zero
  2. (B) Increase by up to about 20%
  3. (C) Stay exactly the same
  4. (D) Reverse direction

Answer: (B) Hyperglycaemia increases SGLT2 expression and activity, raising reabsorption by up to about 20% [1].

Q4. SGLT2 inhibitors lower blood glucose by:
  1. (A) Increasing insulin release
  2. (B) Causing glucose to be excreted in the urine
  3. (C) Blocking gut absorption
  4. (D) Stopping liver glycogen breakdown

Answer: (B) Blocking SGLT2 reduces glucose reabsorption, independent of insulin [1].

Q5. In DAPA-HF, worsening heart failure or cardiovascular death occurred in:
  1. (A) 16.3% with dapagliflozin vs 21.2% with placebo
  2. (B) 21.2% with dapagliflozin vs 16.3% with placebo
  3. (C) The same in both groups
  4. (D) Only in patients with diabetes

Answer: (A) Dapagliflozin reduced the primary outcome, hazard ratio 0.74 [2].

Q6. Were the benefits of dapagliflozin limited to patients with diabetes?
  1. (A) Yes
  2. (B) No, findings were similar with and without diabetes
  3. (C) It harmed non-diabetic patients
  4. (D) Not reported

Answer: (B) Results in patients without diabetes were similar [2].

Q7. In DAPA-HF, adverse events related to volume depletion were:
  1. (A) Much more common with dapagliflozin
  2. (B) Not different between groups
  3. (C) Never recorded
  4. (D) Fatal in most cases

Answer: (B) Volume depletion, renal dysfunction and hypoglycaemia events did not differ [2].

Q8. The energy for most tubular reabsorption comes from:
  1. (A) The Na/K ATPase on the blood side of tubule cells
  2. (B) Gravity
  3. (C) Filtration pressure alone
  4. (D) Bile

Answer: (A) Low intracellular sodium created by the pump drives co-transporters such as SGLT2 [1].

Q9. Glucose appears in the urine when:
  1. (A) Plasma glucose is normal
  2. (B) The filtered load exceeds the transport maximum
  3. (C) GFR falls to zero
  4. (D) Water intake is high

Answer: (B) Once transporters are saturated, glucose spills into the urine; SGLT2 sets most of this capacity [1].

Q10. Over what median follow-up were the DAPA-HF results observed?
  1. (A) 2 weeks
  2. (B) About 18 months
  3. (C) 10 years
  4. (D) 1 day

Answer: (B) Median follow-up was 18.2 months [2].

Quick review

Key takeaways

  • Excreted = filtered − reabsorbed + secreted.
  • Proximal tubule: about two thirds of sodium and water, all glucose.
  • Na/K ATPase powers secondary active transport.
  • SGLT2 carries about 90% of filtered glucose; threshold about 180–200 mg/dL [1].
  • Aldosterone controls potassium secretion in the collecting duct.
  • Dapagliflozin reduces heart failure events [2].

Further reading

SourceWhy it earns its place
DeFronzo RA et al. — Diabetes Obes Metab, 2012The kidney and glucose [1]
McMurray JJV et al. — NEJM, 2019SGLT2 inhibition in heart failure [2]
Eaton DC, Pooler JP — Vander’s Renal PhysiologyTubular transport explained

References

  1. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes, Obesity and Metabolism. 2012;14(1):5–14. doi:10.1111/j.1463-1326.2011.01511.x PMID 21955459 Review
  2. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. New England Journal of Medicine. 2019;381(21):1995–2008. doi:10.1056/NEJMoa1911303 PMID 31535829 Randomised controlled trial

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Reviewed by the Physiotherapist India Team. · Human Physiology contents