Renal Blood Flow and Glomerular Filtration

• What are the three key Starling forces that determine the net flow of fluid at the glomerulus?

  1. Hydrostatic pressure in the glomerular capillaries (Pgc):

  • The blood pressure within the glomerular capillaries that forces fluid out of the capillaries and into the Bowman's capsule.
  • It promotes filtration.

  1. Colloid osmotic pressure in the glomerular capillaries (πgc):

  • The osmotic pressure exerted by proteins (mainly albumin) in the blood plasma.
  • It opposes filtration by drawing fluid back into the capillaries.

  1. Hydrostatic pressure in the Bowman's capsule (Pbs):

  • The pressure exerted by the fluid already in the Bowman's capsule.
  • It opposes filtration by pushing fluid back into the capillaries.
• How does the hydrostatic pressure in the glomerular capillaries (Pgc) influence glomerular filtration?

  • Pgc is the blood pressure within the glomerular capillaries, typically around 55 mmHg.
  • It is the primary driving force for fluid filtration from the glomerular capillaries into the Bowman's capsule.
  • This force is the main contributor to the filtration process, promoting fluid movement out of the blood and into the nephron.
• How does the colloid osmotic pressure in the glomerular capillaries (πgc) influence glomerular filtration?

  • πgc refers to the osmotic pressure created by plasma proteins, such as albumin, which are too large to pass through the capillary walls.
  • The normal value is about 30 mmHg, and it opposes filtration by drawing water back into the capillaries.
  • The greater the concentration of proteins, the stronger the osmotic pull, opposing the outward movement of water.
• How does the hydrostatic pressure in the Bowman's capsule (Pbs) influence glomerular filtration?

  • Pbs is the pressure exerted by the fluid already present in the Bowman's capsule, typically around 15 mmHg.
  • It opposes filtration by resisting the flow of fluid into the capsule.
  • Increased pressure in the Bowman's capsule can reduce the net filtration rate.
• What is the net filtration pressure (NFP) in glomerular filtration?

  • The net filtration pressure (NFP) is the sum of all the forces that drive fluid across the glomerular membrane.
  • It is calculated as:NFP = Pgc - (πgc + Pbs)
  • A positive NFP promotes filtration, while a negative or reduced NFP would reduce filtration.
• What is the role of the fenestrations in the endothelial cells of the glomerular capillaries in the filtration process?

  • Fenestrations are small pores within the endothelial cells of the glomerular capillaries.
  • These pores allow the passage of water, small solutes, and ions from the blood plasma into the glomerular filtrate, but prevent the passage of larger molecules like blood cells and platelets.
  • Fenestrations act as the first filter in the glomerular filtration process.
• How does the basement membrane contribute to the glomerular filtration barrier?

  • The basement membrane is a dense, negatively charged layer of extracellular matrix between the endothelial cells of the capillaries and the podocytes.
  • It acts as a second filter by preventing the passage of large proteins (e.g., albumin) due to its size and charge properties. The negative charge also repels negatively charged molecules, further controlling filtration
• What are filtration slits, and how do they function in the glomerular filtration process?

  • Filtration slits are narrow gaps formed by the interdigitating foot processes of podocytes (specialised epithelial cells surrounding the glomerular capillaries).
  • These slits are covered by a thin diaphragm that further restricts the passage of large molecules, such as proteins.
  • The filtration slits act as the third filter, ensuring that only small molecules and water pass into the glomerular filtrate.
• How do the fenestrations, basement membrane, and filtration slits work together to control which molecules pass into the glomerular filtrate?

  • Fenestrations allow the passage of small solutes and water, while blocking blood cells.
  • Basement membrane further restricts larger molecules, especially proteins, from entering the filtrate due to its size and negative charge.
  • Filtration slits formed by podocytes provide the final barrier, blocking large proteins and other large macromolecules while allowing smaller molecules, such as glucose and electrolytes, to pass.
• What molecules are most likely to pass through the glomerular filtration barrier and into the filtrate?

  Small molecules such as water, glucose, amino acids, ions (e.g., sodium, potassium), and small waste products (e.g., urea) are most likely to pass through the glomerular filtration barrier into the filtrate. Large molecules like proteins and blood cells are largely excluded from the filtrate.
• What would happen if the fenestrations, basement membrane, or filtration slits were damaged?

  Damage to any of these filtration barriers could compromise their selective permeability.

  • Damaged fenestrations may allow larger molecules like blood cells to pass through, leading to hematuria (blood in urine).
  • A damaged basement membrane may result in the leakage of proteins into the filtrate, causing proteinuria (excess protein in urine).
  • Damaged filtration slits may also lead to proteinuria and reduced ability to filter out unwanted substances properly.
• Describe the structure of the filtration slit diaphragm in the podocytes.

  • The filtration slit diaphragm is a thin, proteinaceous structure that spans the filtration slits formed between the foot processes of podocytes.
  • It contains key proteins like nephrin and podocin, which help maintain the barrier function.
  • This diaphragm selectively filters out larger molecules, such as proteins, from entering the filtrate.
•  What is the Bayliss myogenic response?

  An intrinsic mechanism where vascular smooth muscle in the afferent arteriole contracts in response to increased blood pressure, maintaining stable glomerular filtration.
• How does the Bayliss myogenic response protect the glomerular capillaries?

  Prevents excessive increases in glomerular pressure by causing vasoconstriction when blood pressure rises and vasodilation when blood pressure drops.
• What ion channels are involved in the Bayliss myogenic response?

  Stretch-activated ion channels allow Ca²⁺ influx, leading to smooth muscle contraction in response to high pressure.
• What is tubuloglomerular feedback (TGF)?

  An intrinsic autoregulatory mechanism where the macula densa senses NaCl levels in the distal tubule and adjusts afferent arteriole tone to regulate glomerular filtration rate (GFR).
• What happens in TGF when NaCl concentration is high?

  The macula densa signals the afferent arteriole to constrict via ATP/adenosine release, reducing GFR.
• What happens in TGF when NaCl concentration is low?

  The macula densa signals afferent arteriole dilation and stimulates renin release from juxtaglomerular cells, increasing GFR.
• What is the role of ATP and adenosine in TGF?

  ATP and adenosine cause vasoconstriction of the afferent arteriole when NaCl levels are high, reducing GFR.
• Why is intrinsic autoregulation important in the kidneys?

  It ensures stable GFR despite fluctuations in systemic blood pressure, preventing damage to the glomeruli and maintaining filtration efficiency.
• What two mechanisms are responsible for intrinsic renal autoregulation?

  The Bayliss myogenic response and tubuloglomerular feedback (TGF).
• How does the sympathetic nervous system affect renal blood flow?

  Increased sympathetic activity causes vasoconstriction of the afferent arteriole, reducing GFR to conserve fluids during stress.
• How does the renin-angiotensin-aldosterone system (RAAS) influence renal blood pressure?

  Low blood pressure triggers renin release, leading to angiotensin II production, which constricts the efferent arteriole, increasing GFR.
• How does atrial natriuretic peptide (ANP) affect renal blood pressure?

  ANP is released in response to high blood volume, causing afferent arteriole dilation and efferent arteriole constriction to increase GFR and promote sodium excretion.
• What is nephrotic syndrome?

  Nephrotic syndrome is a kidney disorder characterised by excessive protein loss in the urine due to increased glomerular permeability, leading to hypoalbuminemia, oedema, hyperlipidaemia, and increased risk of infections and thrombosis.
• What causes glomeruli to become leaky in nephrotic syndrome?

  Damage to the glomerular filtration barrier, including podocyte injury, loss of negative charge in the basement membrane, and increased permeability, allows large proteins like albumin to pass into the urine (proteinuria).
• Why does hypoalbuminemia occur in nephrotic syndrome?

  Excessive loss of albumin in urine reduces plasma oncotic pressure, leading to fluid leakage into interstitial spaces and causing oedema.
• How does nephrotic syndrome lead to oedema?

  • Low plasma oncotic pressure due to hypoalbuminemia reduces fluid reabsorption into capillaries.
  • The kidneys activate the renin-angiotensin-aldosterone system (RAAS), increasing sodium and water retention.
  • The result is widespread fluid accumulation (oedema).
• Why are patients with nephrotic syndrome at increased risk of thrombosis?

  Loss of anticoagulant proteins (e.g., antithrombin III) in urine leads to a hypercoagulable state, increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism.
• What is glomerulonephritis?

  Glomerulonephritis (GN) is inflammation of the glomeruli, often due to immune-mediated damage, leading to reduced kidney function, hematuria, proteinuria, and hypertension.
• What happens when glomeruli cease to function in glomerulonephritis?

  Loss of glomerular filtration leads to accumulation of waste products (e.g., urea, creatinine), fluid retention, hypertension, and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD).
• How does glomerulonephritis cause haematuria?

  Inflammation and damage to the glomerular capillaries allow red blood cells to leak into the urine, causing haematuria (often with a "cola-coloured" appearance).
• Why does glomerulonephritis lead to hypertension?

  Decreased glomerular filtration and sodium retention activate the RAAS, causing vasoconstriction and increased blood volume, leading to hypertension.
• Compare protein loss in nephrotic syndrome vs. glomerulonephritis.

  • Glomerulonephritis: Mild-to-moderate proteinuria (<3.5g/day) due to inflammation and structural damage.
  • Nephrotic syndrome: Massive proteinuria (>3.5g/day) due to increased glomerular permeability.
• How do nephrotic syndrome and glomerulonephritis affect kidney function over time?

  • Glomerulonephritis: Progressive inflammation can cause scarring (glomerulosclerosis), leading to ESRD requiring dialysis or transplant.
  • Nephrotic syndrome: Chronic protein loss and glomerular damage can lead to CKD.