Glomerulus

1. Overview

The glomerulus is a specialized tuft of capillaries located at the beginning of each nephron in the kidney. It serves as the primary site of blood filtration, initiating urine formation. Surrounded by Bowman’s capsule, the glomerulus forms the renal corpuscle, where water and small solutes are filtered from the blood into the nephron, while cells and large proteins remain in the circulation. This selective filtration is critical to maintaining fluid and electrolyte balance in the body.

2. Location

The glomerulus is located in the renal cortex, inside the renal corpuscle. Each nephron contains one glomerulus. It lies between the afferent arteriole (which supplies blood to the glomerulus) and the efferent arteriole (which drains blood away). These arterioles enter and exit the glomerulus at the vascular pole of the renal corpuscle, while the urinary pole marks the transition to the proximal convoluted tubule.

3. Structure

The glomerulus consists of a network of fenestrated capillaries supported by mesangial cells and surrounded by Bowman’s capsule. Its components include:

• Capillary Endothelium: Fenestrated (has pores) to allow passage of plasma but not cells.

• Basement Membrane: A shared, triple-layered structure that acts as a physical and charge-selective barrier to macromolecules like proteins.

• Podocytes: Specialized epithelial cells in the visceral layer of Bowman’s capsule that wrap around capillaries and form filtration slits between their foot processes (pedicels).

• Mesangial Cells: Located between capillaries; they provide structural support, phagocytose debris, and regulate capillary blood flow.

Filtration Barrier Components:

• Fenestrated capillary endothelium

• Glomerular basement membrane (GBM)

• Slit diaphragm between podocyte foot processes

4. Function

The primary function of the glomerulus is to filter plasma to form glomerular filtrate, the precursor to urine. Specific roles include:

• Selective filtration: Allows water, glucose, amino acids, urea, and small ions to pass while excluding large proteins and blood cells.

• Regulation of filtration rate: Via afferent and efferent arteriole tone and intraglomerular pressure.

• Maintaining systemic homeostasis: Indirectly regulates blood pressure, pH, and osmolarity through filtration and downstream nephron function.

5. Physiological Role(s)

The glomerulus plays a foundational role in renal physiology and systemic balance:

• Maintains glomerular filtration rate (GFR): Ensures stable fluid and solute balance under varying systemic conditions.

• Autoregulation: The glomerulus works with the juxtaglomerular apparatus to adjust afferent and efferent arteriole tone based on blood pressure and sodium delivery.

• Pressure filtration: Blood pressure drives plasma through the filtration barrier, initiating urine formation.

• Volume control: Filters roughly 125 mL of plasma per minute (~180 liters/day), with over 99% reabsorbed downstream in the nephron.

6. Clinical Significance

Glomerulonephritis

Inflammation of the glomerulus due to autoimmune, infectious, or idiopathic causes. Can be acute or chronic and presents with:

• Hematuria

• Proteinuria

• Edema

• Hypertension

Biopsy may show basement membrane thickening, crescent formation, or mesangial proliferation depending on subtype.

Nephrotic Syndrome

Characterized by significant proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia. Caused by glomerular diseases like:

• Minimal change disease (podocyte damage)

• Focal segmental glomerulosclerosis (FSGS)

• Membranous nephropathy

Nephritic Syndrome

Presents with hematuria, mild proteinuria, hypertension, and reduced GFR. Often caused by immune-mediated glomerular injury (e.g., post-streptococcal GN, lupus nephritis).

Diabetic Nephropathy

Chronic hyperglycemia causes thickening of the glomerular basement membrane, podocyte loss, and eventual glomerular sclerosis. Early detection via microalbuminuria screening is critical.

Hypertension-Related Injury

Chronic hypertension can damage the glomeruli (benign nephrosclerosis), while malignant hypertension can cause fibrinoid necrosis and collapse of glomerular structures.

Glomerular Filtration Rate (GFR) Monitoring

GFR is a key indicator of kidney function, often estimated using serum creatinine. Declining GFR indicates progressive glomerular dysfunction and guides staging of chronic kidney disease (CKD).

Congenital Abnormalities

Genetic disorders like Alport syndrome affect glomerular basement membrane integrity, causing progressive renal failure, hematuria, and hearing loss.