Glomerular Filtration

What is glomerular filtration rate controlled by?

• Net Filtration Pressure
  → Balance between blood pressure and opposing forces in the glomerulus

• Renal Blood Flow & Glomerular Blood Pressure
  → More blood = ↑ GFR; Less blood = ↓ GFR

• Filtration Coefficient (Kf)
  → Depends on the permeability and surface area of the glomerular membrane

• Diameter of Afferent and Efferent Arterioles
  → Afferent dilation or efferent constriction increases GFR
  → Afferent constriction or efferent dilation decreases GFR
  → Controlled partly by podocytes

What is autoregulation?

Autoregulation is the kidney’s ability to maintain a stable glomerular filtration rate (GFR) despite changes in blood pressure.

Key Mechanisms:

• Myogenic Response
  → Blood vessels respond to pressure changes by constricting or dilating (e.g. in the afferent arteriole)

• Tubuloglomerular Feedback
  → Macula densa cells sense salt levels in the distal tubule
  → Release local paracrine signals
  → Adjust the diameter of afferent and efferent arterioles to regulate GFR

What is the role of the nervous system?

Sympathetic nerves release noradrenaline, which causes:

• Constriction of arterioles (especially afferent arterioles)

• ↓ Renal blood flow

• ↓ Glomerular filtration rate (GFR)

What is the role of the hormonal system?

Hormonal (Endocrine) Regulation – Long-Acting Effects:

• Angiotensin II
  → Causes vasoconstriction (especially of efferent arterioles)
  → Helps maintain GFR and blood pressure
  → Stimulates aldosterone release to retain sodium and water

• Prostaglandins
  → Cause vasodilation of renal blood vessels
  → Protect kidney perfusion, especially during stress (e.g. when other vasoconstrictors are active)

What is the effect of renal blood flow on GFR?

• Renal blood flow (RBF) directly affects the glomerular filtration rate (GFR).

• Autoregulation keeps GFR stable when systolic blood pressure is between ~90–180 mmHg.

• This is done by adjusting renal vascular resistance (RVR).

• RVR is controlled by changing the diameter (tension) of the afferent and efferent arterioles

What is Renal Vascular Resistance (RVR)?

• RVR refers to the resistance to blood flow in the kidneys.

• It is controlled by the diameter (tension) of the:

  • Afferent arteriole (brings blood to the glomerulus)

  • Efferent arteriole (carries blood away)

Why it matters:

• RVR helps regulate renal blood flow (RBF) and glomerular filtration rate (GFR).

How are renal sympathetic nerves activated?

• Triggered during stressful conditions like:

  • Cold

  • Fear

  • Pain

  • Haemorrhage

  • Vigorous exercise

Purpose:

• Acts as an emergency response to:

  • Increase systemic vascular resistance

  • Maintain blood pressure (even with fluid loss, e.g. sweating or bleeding)

Consequences:

• Short-term: Helps preserve blood pressure

• Long-term (if persistent):

  • Reduces renal blood flow

  • Lowers GFR

  • Risk of renal failure

What is the clinical use of GFR?

Purpose:

• Evaluates kidney function by measuring how well the kidneys filter the blood.

What it tells us:

• How efficiently substances are cleared by the glomeruli

• Gives an indication of nephron function

Important notes:

• GFR is useful for monitoring kidney function

• It does not diagnose specific kidney diseases

Filters out:

• Substances like alcohol, caffeine, and cortisol (stress hormone)

What is GFR estimation?

What it is:

• A way to measure kidney function using a substance cleared by the kidneys

How it’s done:

• Uses either an administered (exogenous) or natural (endogenous) substance

The substance must:

• Be in stable concentration in plasma (not made or broken down in the body)

• Be inert (not reacting or disappearing)

• Be freely filtered at the glomerulus (not bound or charged—e.g. not albumin)

• Not be reabsorbed, secreted, or metabolized in the kidney

Key principle:

Filtered S = Excreted S

Formula:

GFR × [S]plasma = [S]urine × urine flow rate (V)

eGFR:

• Estimated GFR is calculated from:

  • Age

  • Sex

  • Blood creatinine

  • Ethnicity adjustments may apply

What is creatinine?

Key Points:

• Creatinine is a waste product from the breakdown of creatine phosphate in muscles

• Produced at a constant rate, depending on muscle mass

In the kidney:

• Freely filtered at the glomerulus

• Very little is secreted by the proximal convoluted tubule

• Not reabsorbed

Clinical use:

• Because it’s filtered and barely handled otherwise, creatinine levels are used to estimate GFR