Ultrafiltration and Selective Reabsorption

Spec Mapping — OCR H420 Module 5.1.2 — Excretion, content statements covering ultrafiltration at the glomerulus (the three-layer filtration barrier and the role of hydrostatic pressure) and selective reabsorption in the proximal convoluted tubule (cotransport, Na⁺/K⁺ pumps, brush-border specialisation) (refer to the official OCR H420 specification document for exact wording).

Urine formation begins with two key processes: ultrafiltration in the glomerulus, which indiscriminately drives small molecules out of the blood, and selective reabsorption in the proximal convoluted tubule, which rescues almost all the useful substances from the filtrate before the loop of Henle. Together, they ensure that the kidney can handle enormous volumes of blood quickly while still preserving the body's stores of glucose, amino acids, ions and water. This lesson examines both processes at the molecular level, matching OCR A-Level Biology A specification module 5.1.2(f)–(g).

The numerical scale of these processes is striking. A healthy adult kidney pair filters approximately 125 cm³ of plasma per minute — about 180 L per day, roughly 60 times the total plasma volume. Of this, only about 1.5 L is excreted; the other ~99 % is reabsorbed. The system has to be both fast (filtering vast volumes through tiny pores) and selective (rescuing every gram of filtered glucose and almost every gram of filtered amino acid). It achieves both feats through the three-layer filtration barrier at the glomerulus and the densely packed brush-border epithelium of the proximal convoluted tubule. This lesson explores how each works.

Key Definitions:

• Ultrafiltration — the high-pressure filtration of blood plasma through a specialised basement membrane, producing glomerular filtrate.
• Glomerular filtrate — fluid entering the Bowman's capsule after ultrafiltration. It contains water, glucose, amino acids, ions and urea, but not red blood cells or large proteins.
• Selective reabsorption — the return of specific substances from the filtrate back into the blood, particularly in the proximal convoluted tubule.
• Podocyte — a specialised cell of Bowman's capsule whose finger-like processes form filtration slits around the glomerular capillaries.

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Ultrafiltration in the Glomerulus

Ultrafiltration is a passive process, but it requires very high hydrostatic pressure in the glomerulus — much higher than in ordinary capillaries. Three structural features combine to create this pressure and to filter selectively based on size.

Why the Glomerulus Has Such a High Pressure

• The afferent arteriole supplying the glomerulus is wider than the efferent arteriole that drains it. Blood therefore arrives quickly but leaves slowly, causing a back-up of blood that raises hydrostatic pressure in the glomerular capillaries to ~55 mmHg (about three times a normal capillary).
• The glomerulus is a tight capillary knot, offering a large surface area for filtration.
• The renal arteries are short and wide, so blood arrives with little loss of pressure from the aorta.

The resulting high pressure forces water and small solutes out through the filtration barrier into the Bowman's capsule.

The Three-Layer Filtration Barrier

The barrier between the glomerular blood and the capsular space has three layers:

1. Fenestrated capillary endothelium. The endothelial cells of the glomerulus have pores (fenestrations) about 70–100 nm across. These allow plasma fluid and solutes to leave readily but block red blood cells, white blood cells and platelets.
2. Basement membrane. A delicate mesh of collagen and glycoproteins (notably laminin and heparan sulphate) stretches between the capillary endothelium and the podocytes. It acts as the main sieve, blocking molecules larger than about 69 kDa (the size of albumin) and negatively charged proteins by electrostatic repulsion. This is the key selective barrier.
3. Podocytes. The inner layer of Bowman's capsule is formed by podocytes, cells with long processes (pedicels or "foot processes") that interdigitate over the surface of the glomerular capillaries. Between adjacent pedicels are narrow filtration slits about 25 nm wide, covered by a thin slit diaphragm that adds a final sieve.

flowchart LR
    A["Blood plasma in<br/>glomerular capillary"] --> B["Fenestrated endothelium<br/>~70-100 nm pores"]
    B --> C["Basement membrane<br/>main sieve"]
    C --> D["Podocyte filtration slits<br/>~25 nm"]
    D --> E["Capsular space<br/>glomerular filtrate"]

What Crosses and What Doesn't

• Crosses freely: water, glucose, amino acids, urea, inorganic ions (Na⁺, K⁺, Cl⁻, HCO₃⁻), creatinine, small hormones.
• Does not cross: red blood cells, white blood cells, platelets, plasma proteins (albumin, globulins, fibrinogen), any molecule bound tightly to these proteins (some hormones, free fatty acids).

The glomerular filtrate therefore has the same composition as plasma except that it contains no cells and almost no protein.

The Glomerular Filtration Rate (GFR)

In a human, the GFR is about 125 cm³ min⁻¹ (180 L day⁻¹). This is a colossal volume — roughly 60 times the circulating plasma volume per day. Clearly, almost all of it must be reabsorbed: only about 1.5 L is excreted as urine each day.

Net Filtration Pressure

Not all of the hydrostatic pressure drives filtration. Opposing forces reduce it:

• Hydrostatic pressure of the blood in the glomerulus: ~55 mmHg, pushes fluid out.
• Hydrostatic pressure of filtrate in the capsule: ~15 mmHg, pushes fluid back.
• Water potential of blood (made negative by plasma proteins): ~−30 mmHg (equivalent to osmotic pressure), pulls water back.

The net filtration pressure is therefore:

$55 - 15 - 30 = +10 \text{ mmHg}$55−15−30=+10 mmHg

This modest net pressure, across the enormous surface area of the glomerular capillaries, produces the 125 cm³ min⁻¹ GFR.

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Selective Reabsorption in the Proximal Convoluted Tubule

The filtrate leaving the Bowman's capsule is essentially deproteinised plasma — it contains too much of everything useful. The proximal convoluted tubule (PCT) must now rescue:

• ~100 % of the filtered glucose.
• ~100 % of the filtered amino acids.
• ~85 % of the filtered Na⁺, Cl⁻ and water.
• Most of the filtered HCO₃⁻ (for pH balance).
• Some of the filtered urea.

This massive reabsorptive task requires highly specialised cells.

PCT Cell Structure

The PCT is lined by cuboidal epithelial cells adapted for active transport:

• Microvilli on the apical (luminal) surface form a brush border, increasing surface area ~40-fold.
• Many mitochondria, providing ATP for the numerous active transport pumps.
• Basal infoldings increase the surface area on the blood-facing side for the Na⁺/K⁺ pumps.
• Tight junctions between adjacent cells prevent solutes leaking back into the tubule lumen.
• Many co-transporter proteins in the apical membrane, specific for glucose, amino acids, and ions.

The Sodium Gradient and Cotransport

Almost all reabsorption in the PCT is driven by the sodium gradient maintained by Na⁺/K⁺ pumps on the basolateral membrane. The process is:

1. Na⁺/K⁺ pumps on the basolateral membrane actively export 3 Na⁺ out of the cell for every 2 K⁺ pumped in, using ATP. This lowers intracellular [Na⁺].
2. Sodium enters the apical membrane down its concentration gradient, via a variety of cotransporter proteins. Each type of cotransporter carries a useful molecule with it:
   • SGLT (sodium-glucose linked transporters): carry glucose into the cell with Na⁺.
   • Sodium-amino acid cotransporters: carry amino acids with Na⁺.
   • Sodium-phosphate cotransporter: carries phosphate with Na⁺.
3. Glucose and amino acids diffuse out of the basolateral membrane into the blood via facilitated diffusion, down their concentration gradients.
4. Water follows osmotically through aquaporin channels in the apical membrane, because the reabsorption of solutes lowers the water potential on the blood side.
5. Chloride, bicarbonate and urea follow passively.

flowchart LR
    A["PCT lumen<br/>filtrate"] -->|Na+ + glucose<br/>cotransport| B[PCT cell]
    B -->|facilitated diffusion| C[Blood]
    B -->|Na+/K+ pump<br/>ATP| C
    A -->|water by osmosis| C
    A -->|Na+ + amino acid<br/>cotransport| B

Quantitative Aspects

Approximate percentages reabsorbed in the PCT:

Substance	Reabsorbed in PCT	Notes
Glucose	~100 %	Uses SGLT symporters — at high blood glucose (diabetes), the transporter saturates and glucose appears in the urine (glycosuria).
Amino acids	~100 %	Multiple Na⁺-cotransporters.
Na⁺	~65 %	Active transport.
Water	~65 %	Osmosis following solute.
HCO₃⁻	~80 %	Important for blood pH homeostasis.
Urea	~50 %	Passive, following water.
K⁺	~65 %	Paracellular and transcellular.

By the end of the PCT, the filtrate has shrunk to about one-third of its original volume but has almost the same osmotic concentration as plasma (it is iso-osmotic).

The Tubular Maximum

Each carrier has a maximum rate of transport (the tubular maximum or Tm). If the filtered load exceeds this, the excess is not reabsorbed and appears in the urine. For glucose, this is why untreated diabetes mellitus causes glucose to appear in the urine — the filtered glucose exceeds the SGLT Tm.

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Linking Structure to Function

Feature	Role
Wider afferent than efferent arteriole	Maintains high hydrostatic pressure for ultrafiltration
Fenestrated capillary endothelium	Allows plasma fluid and solutes to pass while blocking cells
Basement membrane	Acts as the main molecular sieve; blocks proteins
Podocyte filtration slits	Provide an additional fine sieve
Microvilli on PCT cells	Vast surface area for reabsorption
Mitochondria in PCT cells	ATP for active transport and cotransport
Na⁺/K⁺ pumps on basolateral membrane	Establish Na⁺ gradient that powers cotransport
Tight junctions	Prevent reabsorbed solutes leaking back into filtrate

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Exam Tip

OCR loves to ask "why is glucose found in the urine of a diabetic?" The answer is not simply "because there is more glucose". It is: the high blood glucose leads to a high filtered load that exceeds the Tm of the SGLT transporters in the PCT, so some glucose is not reabsorbed and passes into the urine. Mention saturation of the transporter explicitly to gain full marks.

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Common Exam Mistakes

• Saying large molecules are blocked by the podocytes. The main barrier is the basement membrane; podocytes provide additional selectivity.
• Describing reabsorption of glucose as "active transport". The apical uptake is secondary active transport (cotransport) — glucose moves with Na⁺, not by a glucose-specific ATP pump.
• Forgetting that Na⁺/K⁺ pumps are on the basolateral, not the apical, side. The apical membrane uses cotransporters, not primary pumps.
• Claiming water is actively reabsorbed in the PCT. Water moves by osmosis following the reabsorbed solutes.
• Missing the quantitative aspect. OCR frequently asks about percentages: ~65 % of filtered water, ~100 % of glucose.
• Confusing Bowman's capsule with the glomerulus. The glomerulus is the capillary knot; Bowman's capsule is the surrounding cup.
• Ignoring the tubular maximum. You cannot explain glucose in diabetic urine without it.

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Quick Recap

• Ultrafiltration in the glomerulus is driven by a high hydrostatic pressure created by the afferent arteriole being wider than the efferent.
• The filtration barrier has three layers: fenestrated endothelium, basement membrane (main sieve) and podocyte filtration slits.
• Small molecules (water, glucose, amino acids, ions, urea) cross; blood cells and plasma proteins do not.
• The glomerular filtration rate is ~125 cm³ min⁻¹, producing ~180 L of filtrate per day.
• In the PCT, ~100 % of glucose and amino acids, ~65 % of water and Na⁺, and ~80 % of bicarbonate are reabsorbed.
• Reabsorption in the PCT uses Na⁺-linked cotransport driven by Na⁺/K⁺ pumps on the basolateral side; water follows by osmosis.
• Exceeding a carrier's tubular maximum (e.g., for glucose in diabetes) leaves substances in the urine.

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SVG — Close-Up of the Glomerular Filtration Barrier