Renal L2 - Filtration unit of the kidney

Explain blood flow to the kidney ?

Renal Blood Flow and Filtration in a Healthy Adult

• Renal blood flow: ~1.2 L/min (approximately 650 mL plasma/min)

• Proportion of cardiac output: 20–25%

• Kidney weight: Only 1–2% of total body weight

➡ This ensures a high plasma filtration rate

Plasma and Filtration Volumes

• Total plasma volume: ~3 L

• Glomerular filtration rate (GFR): 125 mL/min or 180 L/day
  ➡ This means the entire plasma volume is filtered ~60 times per day

Physiological Importance

• Allows precise and rapid control of:

  • Fluid volume

  • Electrolyte balance

  • Composition of body fluids

Describe glomerular filtration rate

GFR refers to the rate at which blood is filtered through the glomeruli of the kidneys, totaling approximately 125 mL/min or 180 L/day in a healthy adult, which indicates efficient plasma filtration.

• Glomerular Filtration Rate (GFR) the volume of plasma filtered per minute

• GFR is an important indicator of kidney function.

• GFR declines in kidney disease

What is filtratration Fraction ?

Filtration Fraction (FF): The fraction of the renal plasma flow that is filtered in the glomerulus during a single pass through the kidney = GFR/Renal Plasma flow

• Example:

  • FF = 125 ml/min / 650 ml/min= 0.2 i.e. 20% of plasma flowing through the kidneys is filtered

What are the forces that drive glomerular filtration?

Glomerular capillary pressure

Forces that oppose glomerular filtration:

1. Pressure in glomerular capsule. Glomerular capsule = Bowman’s capsule

2. Osmotic force due to proteins in plasma. plasma osmotic pressure

What drives the formation of glomerular filtrate into Bowman’s capsule?,

The balance of hydrostatic and osmotic pressures across the glomerular capillary walls.

Which pressure favors filtration?

Glomerular hydrostatic pressure (~55 mmHg), generated by the heart, pushes fluid out of capillaries into Bowman’s capsule.

Which two pressures oppose filtration?

Capsular hydrostatic pressure (~15 mmHg) and blood colloid osmotic pressure (~30 mmHg) both resist fluid movement into the capsule.

What is capsular hydrostatic pressure (CHP)?

The pressure exerted by existing fluid in Bowman’s capsule that pushes against further filtration.

What is blood colloid osmotic pressure (BCOP)?

The osmotic pull exerted by plasma proteins that draws water back into the capillaries.

What is the formula for Net Filtration Pressure (NFP)?

NFP = GHP - (CHP + BCOP)

What is the typical value of Net Filtration Pressure (NFP)?,

The typical value of Net Filtration Pressure (NFP) is approximately 10 mmHg. This value reflects the balance of forces driving filtration in the glomerulus.

What determines glomerular capillary pressure ($P_G$)?

Arterial pressure, afferent arteriolar resistance, and efferent arteriolar resistance

How does increased arterial pressure affect GFR?

Increases glomerular capillary pressure and increases GFR, but renal autoregulation limits this effect

What is the effect of increased afferent arteriolar resistance on GFR?

Decreases glomerular capillary pressure and decreases GFR

What happens to GFR when afferent arteriolar resistance decreases?

Glomerular capillary pressure increases and GFR increases

How does increased efferent arteriolar resistance affect GFR?

Increases glomerular capillary pressure and increases GFR?

What is the effect of decreased efferent arteriolar resistance on GFR?

Decreases glomerular capillary pressure and decreases GFR1

How is GFR measured in clinical practice?

By estimating creatinine clearance:
GFR ≈ (Urine concentration of creatinine × Urine flow rate) / Plasma concentration of creatinine

What characteristics must a molecule have to be used for GFR measurement?

It must be filtered at the glomerulus but not reabsorbed or secreted by the tubules (e.g., creatinine)

What two main factors determine GFR?

Permeability of the glomerular membrane and net filtration pressure?

What is net filtration pressure?

The balance of forces across the glomerular capillary wall, mainly glomerular hydrostatic pressure, plasma oncotic pressure, and Bowman’s capsule hydrostatic pressure

How does severe burns affect GFR?

Loss of plasma proteins lowers plasma oncotic pressure, increasing GFR

How does urinary tract obstruction affect GFR?

Increases Bowman’s capsule hydrostatic pressure, decreasing GFR

How does severe dehydration affect GFR?

Increases plasma oncotic pressure, decreasing GFR

How does Glomerular Filtration Rate change in chronic kidney disease?

• Glomerular Filtration Rate decreases in chronic kidney disease

  • Chronic kidney disease (CKD): Gradual loss of kidney function

  • As GFR cannot be measured directly, current practice is to estimate GFR (eGFR) in patients.

• In end stage renal disease, patients will require kidney replacement therapy, which involves either renal dialysis (haemodialysis or peritoneal) or kidney transplantation. We will discuss this in detail in the workshop next week

• Currently no treatments for CKD. Development of new therapy for CKD is a major focus of my current research program.

What are the 3 components of the glomerular filtration barrier?

– The endothelial cells

– Basement Membrane (-ve charged)

– The Podocyte with their ‘slit diaphragm’

These three components work together to prevent the passage of large molecules and negatively charged proteins from the blood into the urine.

why are Glomerular capillaries more efficient filters than other capillaries?

• very large fenestrations

• high hydrostatic pressures driving filtration (55 vs 18 mmHg)

Why do we need a glomerular filtration barrier?

Filterability of solutes

• Size & Charge

• small molecules (<3nm or 7000MW) filtered freely

• >7-9nm or 70000MW essentially blocked

• Most proteins prevented due to negative charge they carry

Filtrate inside Bowman’s Capsule is virtually identical to plasma but essentially free of protein (0.02%)

how does renal disease affect the glomerular filtration barrier in disease?

Triggers a set of changes in glomerular filtration barrier

that cause a loss of selectivity and result in proteinuria. Eg: Diabetes

What protiens in urine can indicate an underlying renal disease?

Eg: Albumin. Albuminuria is used to detect kidney disease