26th June 2023

Physiology and Pathophysiology of the glomerulus

Physiology of the glomerulus

Glomerulonephritis is caused by inflammation of the glomerulus. The glomerulus is involved in ultrafiltration of the blood (filtration under pressure), regulating renal blood flow and maintenance of systemic blood pressure. The glomerulus is a bundle of capillaries contained within Bowman’s capsule, and together they make up the renal corpuscle. The renal corpuscle filters blood – this happens when blood travels from the afferent arteriole into the glomerulus under pressure. The fenestrated endothelial cells of the glomerular capillaries and podocytes allow water, ions, and small molecules from the bloodstream to flow into Bowman’s capsule and out into the proximal convoluted tubule to eventually be excreted in the urine. Larger molecules, such as proteins and blood cells, are normally unable to pass through the glomerulus and therefore remain within the blood.

Pathophysiology of the glomerulus

In glomerulonephritis, the glomerulus becomes damaged; this can occur due to multiple reasons including immune cells, antibodies, complement proteins, immune complexes, hypertension, and sclerosis. This helps to explain the common presentations of glomerulonephritis which are: asymptomatic proteinuria and haematuria; nephrotic syndrome; nephritic syndrome; rapidly progressive glomerular disease; and chronic kidney disease.

Nephrotic Syndrome

Consists of a triad of:

• Heavy proteinuria (>3.5g/day)
• Hypoalbuminemia
• Oedema

Proteinuria develops due to disruption to the filtering process of the glomerulus, caused by damage to the endothelial cells and podocytes. This results in the passage of proteins into the urine. This process also causes albumin (a protein) to incorrectly pass out of the bloodstream, causing hypoalbuminaemia. Oedema is secondary to low serum albumin, loss of oncotic pressure and retention of sodium and water by the distal nephron.

Patients with nephrotic syndrome are hypercoagulable due to the loss of antithrombin proteins, particularly antithrombin III, in the urine. This increases the risk of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and renal vein thrombosis. Hyperlipidaemia is very common and causes an increased risk of cardiovascular disease. There is also an increased risk of bacterial infection, most commonly cellulitis, due to urinary immunoglobulin loss. Hypocalcaemia can also occur due to the loss of vitamin D and binding protein in the urine.

Nephritic Syndrome

Patients typically present with haematuria (both macroscopic and microscopic), hypertension, proteinuria, and sterile pyuria. It is caused primarily by inflammation and damage to the glomerular capillary.