How does filtration occur in the kidney?

The basic filtration unit of the kidney is the renal corpuscle, consisting of a glomerulus surrounded by a Bowman’s capsule. The high glomerular capillary hydrostatic pressure forces a fraction of the plasma (i.e. water and solutes) through the capillary wall and into the Bowman’s space. This filtration barrier is composed of three layers:

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  Glomerular capillary endothelium, a specialised endothelium with large fenestrations.

  
  
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  Glomerular basement membrane, a layer of supportive basal lamina.

  
  
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  Podocytes, the epithelial cells of a Bowman’s capsule. These cells have foot-like projections that wrap around glomerular capillary endothelial cells, leaving slit-like openings between them.

It is important that filtration permits the passage of water and solutes, but that the capillary retains blood cells and proteins. This selectivity results from:

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  The effective pore size of the glomerular capillaries. This is determined by the size of the capillary wall fenestrations and the spacing between podocyte foot processes:

  
  
  
  
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     – Particles below 7 kDa are freely filtered into the Bowman’s space.

     
     
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     – Particles above 70 kDa (e.g. immunoglobulins – around 150 kDa) cannot pass between through the pores.

     
     
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     – Between 7 and 70 kDa, partial filtration occurs.

  Albumin (67 kDa) is just small enough to fit through the pores, but filtration is prevented due to its negative charge (see below). Haemoglobin (Hb) is a 69.8‑kDa protein, and so is just small enough to be filtered. Hb must therefore be sequestered within red blood cells to prevent filtration.
  
  
  
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  Particle charge. Most plasma proteins are negatively charged, as their pK_a is less than physiological pH. As a result:

  
  
  
  
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     – Plasma proteins are retained. When negatively charged plasma proteins approach the glomerular fenestrations, they are repelled by the negative charges of the glomerular basement membrane and podocyte foot processes.

     
     
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     – Small anions are filtered. Small anions do not come into close enough contact with the glomerular membrane proteins to be repelled.

  
  

A final determinant of whether a particle is filtered is the extent of its binding to plasma proteins: acidic compounds bind to albumin, whilst basic compounds bind to α-1-glycoprotein. The extent of protein binding is an important determinant in the clearance of many drugs.

What happens to the filtrate in the renal tubules?

Filtration results in a tubular fluid that contains not only metabolic waste products, but also useful solutes such as electrolytes, glucose and amino acids. The nephron reabsorbs these essential components.

Most of the reabsorption occurs in the proximal convoluted tubule (PCT). Here, 67% of Na⁺, K⁺, Cl‾ and water, 85% of HCO₃‾ and (in normal subjects) 100% of glucose and amino acids are reabsorbed. Reabsorption takes place through active or passive processes:

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  Active reabsorption. The reabsorption of most substances is active (i.e. requires energy), accounting for the high metabolic activity of the kidney. In the basolateral membrane of the tubular cells, Na⁺/K⁺-ATPase ion pumps actively extrude Na⁺ ions from the tubular cells into the peritubular capillaries in exchange for K⁺. The resulting low intracellular Na⁺ concentration is used to drive:

  
  
  
  
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     – Co-transporters: for example, the sodium–glucose-linked transporter (SGLT2) responsible for glucose reabsorption;

     
     
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     – Counter-transporters: for example, the Na⁺/H⁺ counter-transporter, which is involved in acid excretion.

  
  
  
  
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  Passive reabsorption. Water is reabsorbed passively: the balance of Starling forces favours bulk reabsorption of water (see Chapter 36). Some of the dissolved electrolytes and small molecules such as urea are passively reabsorbed with water.

Figure 68.1 Reabsorption of glucose in the proximal convoluted tubule.

How else may substances be renally excreted?

The PCT also actively secretes waste products into the tubular filtrate. Secretion is an active, energy-consuming process in which substances are transported from the peritubular capillaries to the PCT. It allows more effective excretion of waste products than filtration alone. Of clinical importance, many drugs are cleared from the blood with the aid of active secretion through two different carriers:

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  The organic anion transporter, which secretes a number endogenous and exogenous anionic substances, such as uric acid, penicillin, probenecid and aspirin. Because the same transporter is used for all substances and has a limited capacity for secretion, the presence of one substance affects the clearance of another. For example, probenecid is secreted by the anion transporter in preference to penicillin; co-administration therefore reduces the clearance of penicillin. This pharmacological interaction was exploited during World War II, when penicillin supplies were limited.

  
  
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  The organic cation transporter, which secretes a number of important cationic substances, such as creatinine, catecholamines and morphine.