Welcome to the Kidney: Structure and Function Explained

🩺 What the Kidneys Might Be Telling Us

A 56-year-old woman visits her GP with two common but vague symptoms: fatigue and ankle swelling. Her vitals and labs show:

• Blood pressure: 152/88 mmHg 
• Creatinine: 145 µmol/L
• eGFR: 42 mL/min/1.73m²
• Haemoglobin: Mild normocytic anaemia
• Urine dipstick: 1+ protein, no blood

As a GP, I'd be asking: are these early signs of chronic kidney disease (CKD), or part of a broader hypertensive picture? These results might seem only mildly abnormal, but even “moderate” kidney dysfunction can signal serious shifts in physiology. So—what’s failing? And why do those failures affect more than just the urine?

This post walks through how each part of the nephron contributes to health, and what happens when that function begins to slip.

🔬 From Big Picture to Fine Detail: Structure Shapes Function

The kidneys aren’t just high-end filters—they’re endocrine, regulatory, and excretory organs that respond dynamically to the body’s needs. They weigh up salt, acid, fluid, pressure, oxygen-carrying capacity—and make judgment calls every second.

Each kidney contains:

• A cortex, where blood is filtered and nutrients are reabsorbed
• A medulla, where the body’s water conservation system is fine-tuned
• A funnel-like pelvis and ureter, for controlled urine transport

Running through this structure are about 1 million nephrons per kidney—tiny, self-contained processing units that together maintain internal balance. Let’s follow the path of filtered blood through each nephron segment—and trace how dysfunction in each one explains our patient’s symptoms.

🧪 Step 1: The Glomerulus—Letting the Right Stuff In

Where is it?
In the renal cortex, inside Bowman’s capsule

What happens here?

Blood pressure drives plasma across a three-layer filter:

1. Fenestrated endothelium (leaky capillaries)
2. Basement membrane
3. Podocyte slit diaphragms

This sieve allows water, electrolytes, glucose, and small proteins to pass—but retains cells and larger proteins.

🧭 Why this matters:

If this barrier is damaged, protein leaks into the urine. Our patient’s 1+ proteinuria suggests early barrier disruption—possibly from hypertension or subtle glomerular injury.

💭 Check your thinking:
Why don’t we see red blood cells? What might that tell us about the site of damage?

⚙️ Step 2: The Proximal Convoluted Tubule—Reclaiming What Matters

Where is it?
Cortex, just downstream from the glomerulus

What happens here?
The PCT reabsorbs:

• ~65% of filtered sodium and water
• ~90% of bicarbonate
• ~100% of glucose and amino acids

It also secretes waste products like creatinine, certain medications, and organic acids.

How?
Sodium-potassium pumps on the blood side create a gradient that pulls sodium from the tubular fluid into cells—bringing water and solutes with it. Bicarbonate is reclaimed through a multi-step reaction involving carbonic anhydrase.

🧭 Why this matters:

This segment prevents massive nutrient loss and helps balance acid-base. If impaired:

• Fluid can build up → mild ankle oedema
• Creatinine clearance drops → lab signs of reduced GFR
• Acid can accumulate, though this may come later

🩺 In our patient: The creatinine elevation and possible early acidosis signal reduced efficiency here.

🌊 Step 3: Loop of Henle—Building the Medullary Gradient

Where is it?
Starts in the cortex, dips deep into the medulla, then loops back up

What happens here?

• Descending limb: permeable to water but not solutes. Water exits into the salty medulla.
• Ascending limb: impermeable to water; actively pumps out Na⁺, K⁺, and Cl⁻, which creates a steep osmotic gradient in the medulla.

This gradient is essential for controlling water reabsorption later on.

🧭 Why this matters:
Without this gradient, the kidney can’t concentrate urine—leading to polyuria and dehydration in more advanced disease or after loop diuretics.

💭 Check your thinking:
If the patient’s sodium and fluid handling becomes impaired, how might that affect their blood pressure or volume status?

🧂 Step 4: Distal Convoluted Tubule—Fine-Tuning Electrolytes

Where is it?
Back in the cortex, after the Loop of Henle

What happens here?
This is the hormone-sensitive zone:

• Aldosterone increases sodium reabsorption and potassium secretion.
• Parathyroid hormone (PTH) promotes calcium reabsorption.
• It also plays a small role in acid-base balance.

🧭 Why this matters:
Dysfunction here may lead to:

• Hyperkalaemia (dangerous in CKD)
• Metabolic alkalosis or hypocalcaemia
• Impaired blood pressure and volume regulation

🩺 In our patient: Her elevated BP and proteinuria suggest RAAS overactivation. This segment is likely responding to (or contributing to) that hormonal cascade.

🚰 Step 5: Collecting Duct—Making the Final Call

Where is it?
Traverses both cortex and medulla

What happens here?

• Water reabsorption is controlled by antidiuretic hormone (ADH), which inserts water channels (aquaporins) into the duct wall.
• Urea recycling contributes to medullary tonicity.
• Hydrogen ions are secreted for acid-base control.

🧭 Why this matters:This is where the nephron decides whether to produce dilute or concentrated urine. When GFR falls or medullary gradients weaken, urine becomes less adaptable to hydration needs.

🩺 In our patient: If ADH is high (as in volume depletion), water reabsorption increases—but if this system is impaired, fluid balance becomes unpredictable, contributing to oedema or hypo/hypernatraemia.

Test yourself - interactive table 

Take a moment to check your understanding of each nephron segment—not just what it does, but what could happen if it stops working properly. Try filling in the right handcolumn yourself before revealing the answer.

Nephron Segment	What does it normally do?	What happens if this fails?
Glomerulus	Filters plasma into Bowman’s capsule
Proximal Tubule	Reabsorbs Na⁺, water, glucose, bicarbonate; secretes creatinine
Loop of Henle	Creates medullary salt gradient to concentrate urine
Distal Tubule	Hormonal salt and pH tuning via aldosterone / PTH
Collecting Duct	Final water and acid-base balance tuning via ADH

🔄 Pulling It All Together: Why Small Changes Matter

Let’s revisit the patient’s symptoms and match them to potential mechanisms:

Symptom / Finding	Likely Renal Cause
Fatigue	Decreased erythropoietin production (cortical interstitial cells)
Mild oedema	Impaired sodium/water handling (PCT, DCT, collecting duct)
Proteinuria	Glomerular barrier leakage
Normocytic anaemia	Erythropoietin deficiency
High BP	RAAS overactivation, sodium retention
Elevated creatinine	Reduced filtration + secretion efficiency

Reflection prompt:

If our patient’s GFR fell to 20, what additional symptoms or complications might you expect—and which nephron segments would be involved?

🧪 Try It Yourself: Building from First Principles

Here’s a challenge to extend your reasoning:

Case prompt: A 28-year-old man presents with excessive urination and extreme thirst. His serum sodium is 149 mmol/L, and urine osmolality is low.

• How might the function of the nephron’s medulla or collecting duct explain these findings?
• What hormones or signalling pathways might be impaired?

💭 Think about:

• Where in the nephron water is conserved
• What role ADH plays
• What would happen if the countercurrent gradient were disrupted

✨ Bonus twist: How would this presentation differ if the patient’s sodium were low instead?

• 📝 Complete the quiz on this topic →
• 📝 All posts on the renal / urinary system →