Glomerular Filtration

Glomerular filtration is the first and most fundamental step in the formation of urine, performed by the kidneys to maintain the body’s internal environment. This process occurs in the renal corpuscle, which consists of a cluster of specialized capillaries called the glomerulus surrounded by Bowman’s capsule. When blood enters the glomerulus through the afferent arteriole, it is subjected to a relatively high hydrostatic pressure. This pressure forces water and small dissolved substances out of the blood and into Bowman’s capsule, while larger components such as proteins and blood cells remain in the circulation.

The filtration that takes place is not random; it is regulated by a three-layered filtration barrier composed of the capillary endothelium, the basement membrane, and the podocyte layer of Bowman’s capsule. These layers allow free passage of water, ions, glucose, amino acids, and other small molecules, but restrict large plasma proteins and cellular elements.

Glomerular filtration is essential for eliminating metabolic wastes like urea and creatinine, controlling the volume and composition of body fluids, and maintaining acid–base and electrolyte balance. The amount of fluid filtered per minute is called the glomerular filtration rate (GFR), which is a key indicator of kidney function. In healthy adults, the average GFR is approximately 125 mL/min, resulting in about 180 liters of filtrate being produced each day, most of which is reabsorbed later in the nephron.

Through this highly selective and efficient process, glomerular filtration plays a central role in cleansing the blood and regulating the chemical stability of the body’s internal environment.

Mechanism of Glomerular Filtration

Glomerular filtration is a pressure-driven process that occurs in the renal corpuscle and involves the movement of water and small solutes from the blood into Bowman’s capsule. The mechanism can be explained step by step:

1. Blood Flow to the Glomerulus

Blood enters the kidney through the renal artery, which branches into smaller vessels until it reaches the afferent arteriole. This arteriole delivers blood to the glomerular capillaries. The afferent arteriole has a wider diameter compared to the efferent arteriole, creating a high pressure inside the glomerulus.

2. Filtration Barrier Structure

Filtration occurs across a three-layered barrier:

• Fenestrated Endothelium of Capillaries – Has pores (fenestrations) that allow passage of water and small molecules but prevent blood cells from escaping.
• Basement Membrane – A thick, negatively charged layer that acts as the main filtration barrier, restricting large proteins.
• Podocytes of Bowman’s Capsule – Specialized epithelial cells with foot-like projections forming filtration slits, further controlling what enters the filtrate.

3. Driving Forces of Filtration

The movement of fluid is determined by the net filtration pressure (NFP), which results from the balance of three forces:

1. Glomerular Hydrostatic Pressure (GHP) – Blood pressure within glomerular capillaries (~55 mmHg), pushing fluid out of the blood into Bowman’s capsule.
2. Capsular Hydrostatic Pressure (CHP) – Pressure exerted by the fluid already in Bowman’s capsule (~15 mmHg), opposing filtration.
3. Blood Colloid Osmotic Pressure (BCOP) – Osmotic pull of plasma proteins (~30 mmHg), drawing water back into the capillaries and opposing filtration.

Net Filtration Pressure (NFP)

NFP = Glomerular Hydrostatic Pressure − (Capsular Hydrostatic Pressure + Blood Colloid Osmotic Pressure)

NFP = GHP − (CHP + BCOP)

Example with normal values:

NFP = 55 − (15 + 30) = 10 mmHg

4. Formation of Glomerular Filtrate

Due to this pressure difference, water and dissolved substances like glucose, amino acids, electrolytes, and urea move from the blood into the capsular space. Large plasma proteins and blood cells remain in circulation.

5. Glomerular Filtration Rate (GFR)

The GFR is the volume of filtrate produced per minute. In healthy adults:

• Men: ~125 mL/min
• Women: ~105 mL/min
  This equals about 180 liters/day, but most of this filtrate is reabsorbed in the tubules.

6. Regulation of Filtration

The body regulates GFR through:

• Autoregulation (myogenic mechanism and tubuloglomerular feedback)
• Neural control (sympathetic nervous system)
• Hormonal control (renin–angiotensin–aldosterone system, atrial natriuretic peptide)

Through this finely tuned mechanism, glomerular filtration ensures continuous removal of waste products while preserving essential molecules, keeping the body’s internal environment stable.

Substances Filtered and Not Filtered in Glomerular Filtration

During glomerular filtration, the kidneys act like a highly selective sieve, allowing certain substances to pass from the blood into Bowman’s capsule while restricting others. The selection depends mainly on molecular size, electrical charge, and the structural properties of the glomerular filtration barrier.

1. Substances Filtered

These are small molecules and water-soluble components of plasma that can easily pass through the fenestrated endothelium, basement membrane, and podocyte filtration slits.

a) Water

• Freely filtered due to its small molecular size.
• Makes up the largest component of glomerular filtrate.

b) Electrolytes (Ions)

• Sodium (Na⁺), Potassium (K⁺), Chloride (Cl⁻), Bicarbonate (HCO₃⁻), Calcium (Ca²⁺), Magnesium (Mg²⁺).
• Freely filtered and later regulated through reabsorption or secretion in the tubules.

c) Nitrogenous Wastes

• Urea, creatinine, uric acid, ammonia.
• Freely filtered; most are excreted, though some (like urea) are partially reabsorbed.

d) Nutrients

• Glucose, amino acids, water-soluble vitamins.
• Freely filtered but normally reabsorbed almost completely in the proximal tubule.

e) Small Peptides and Hormones

• Low–molecular weight peptides (e.g., insulin) can be filtered and then degraded in the tubules.

2. Substances Not Filtered

These are larger molecules or structures that the filtration barrier blocks due to size restriction and charge repulsion.

a) Blood Cells

• Red blood cells, white blood cells, platelets.
• Too large to pass through fenestrations; their presence in urine (hematuria) indicates barrier damage.

b) Large Plasma Proteins

• Albumin, globulins, fibrinogen.
• Most are larger than the filtration slit size or are repelled by the negatively charged basement membrane.
• Minimal albumin may pass but is reabsorbed in the proximal tubule; significant albuminuria indicates kidney disease.

c) Large Lipid-Bound Molecules

• Lipoproteins (e.g., LDL, HDL) are too large and hydrophobic for filtration.

d) Protein–Bound Substances

• Many hormones, drugs, and fatty acids bound to plasma proteins are not filtered because the proteins themselves cannot pass.

Category	Examples	Filtration Status
Water	H₂O	Filtered
Electrolytes	Na⁺, K⁺, Cl⁻, HCO₃⁻, Ca²⁺, Mg²⁺	Filtered
Nitrogenous wastes	Urea, creatinine, uric acid, ammonia	Filtered
Nutrients	Glucose, amino acids, vitamins (water-soluble)	Filtered
Small peptides	Insulin, small hormones	Filtered
Blood cells	RBCs, WBCs, platelets	Not filtered
Large proteins	Albumin, globulins, fibrinogen	Not filtered (except trace albumin)
Lipid-bound molecules	LDL, HDL	Not filtered
Protein-bound substances	Steroid hormones, fatty acids	Not filtered

 

Glomerular Filtration Barrier

The glomerular filtration barrier is a specialized, multi-layered structure in the renal corpuscle that allows water and small solutes to pass from the blood into Bowman’s capsule while preventing the loss of large plasma proteins and blood cells. Its unique design ensures selective permeability—working like a highly precise sieve—and plays a crucial role in maintaining the composition of the blood and the filtrate.

This barrier is made of three main layers, each with distinct structural and functional properties:

1. Fenestrated Endothelium of Glomerular Capillaries

• Structure: The innermost layer in contact with blood. It is formed by endothelial cells containing numerous small pores or fenestrations (about 70–100 nanometers in diameter).
• Function:
  • Permits free passage of water, ions, glucose, urea, and other small molecules.
  • Prevents the passage of blood cells (red blood cells, white blood cells, and platelets) due to pore size restriction.
  • Contains negatively charged glycoproteins that repel negatively charged proteins in plasma.

2. Glomerular Basement Membrane (GBM)

• Structure: A thick, gel-like layer situated between the endothelium and podocytes. It is composed of type IV collagen, laminin, proteoglycans, and other matrix proteins.
• Function:
  • Acts as the primary filtration barrier for large molecules, especially plasma proteins like albumin.
  • Possesses a strong negative charge due to heparan sulfate proteoglycans, which repels negatively charged molecules, further restricting protein filtration.
  • Provides mechanical strength and support to the filtration structure.

3. Podocyte Layer (Visceral Epithelium of Bowman’s Capsule)

• Structure: Specialized epithelial cells called podocytes cover the outer surface of the basement membrane. Each podocyte has finger-like extensions called primary processes, which branch into secondary processes or pedicels. Between the pedicels are narrow gaps known as filtration slits.
• Filtration Slit Diaphragm: A thin membrane made of proteins such as nephrin and podocin spans the slits, acting as an additional molecular filter.
• Function:
  • Regulates the final passage of molecules into the filtrate.
  • Provides structural support to the glomerular capillaries.
  • Prevents leakage of plasma proteins into Bowman’s space.

Combined Function of the Barrier

The three layers work together to achieve size-selective and charge-selective filtration:

• Size Selectivity: Allows molecules with a radius < 4 nanometers to pass freely; restricts those > 8 nanometers.
• Charge Selectivity: Negatively charged molecules are restricted more strongly than neutral ones of the same size.

Clinical Significance

Damage to any part of the filtration barrier can cause proteinuria (presence of proteins in urine) or hematuria (blood in urine), which are key signs of kidney disease. Conditions like glomerulonephritis, diabetic nephropathy, and minimal change disease affect different layers of the barrier, compromising its function.