Lesson 39: Glomerular Filtration Rate, Renal Clearance, and Intrarenal Homeostasis

Compare and contrast the chemical composition of plasma to the glomerular filtrate (fluid in Bowman’s space)

• Plasma → contains proteins and blood cells

• Glomerular filtrate → no proteins or blood cells

GFR is tightly regulated to __________________________

GFR is tightly regulated to maintain stable filtration and homeostasis despite changes in blood pressure or fluid balance

GFR is regulated by _________________________

GFR is regulated by neural & hormonal input to afferent & efferent arteriole vascular smooth muscle cells (VSMC) that constrict or dilate to change filtration pressure.

When total-body Na⁺ decreases, how is GFR affected?

↓ Na⁺ → ↓ ECF & BP → Afferent constriction → ↓ GFR → Retain Na⁺ & water → Stabilize BP

When total body Na⁺ increases, how is GFR affected?

↑ Na⁺ → ↑ ECF & BP → Afferent dilation → ↑ GFR → ↑ Na⁺ & water excretion → Lower BP.

Define renal clearance

Renal clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time (usually mL/min)

What is renal clearance’s importance in quantifying renal function?

It shows how effectively the kidneys remove a substance from the blood. By measuring the clearance of specific substances—like inulin (for accurate GFR) or creatinine (for estimated GFR)—clinicians can assess kidney filtration and overall renal function

How can GFR be measured?

• Inulin – freely filtered, not reabsorbed, not secreted (Cl_IN – true GFR)

• Creatinine – freely filtered, not reabsorbed, secreted in small amounts (Cl_Cr – estimated GFR)

What is the flow of filtration?

Renal artery → afferent arteriole → Glomerular capillary → Bowman’s space → proximal tubule → loop of Henle →   distal tubule → collecting duct → renal pelvis → ureter → bladder → urethra

_____________ is the movement of fluid and solutes from glomerular capillaries across barrier into Bowman’s space and occurs due to _________________________. It is also the first step in making urine.

Glomerular filtration is the movement of fluid and solutes from glomerular capillaries across barrier into Bowman’s space and occurs due to Starling Forces. It is also the first step in making urine.

Glomerular filtration is a ____________ process, where ______________ pressures force fluids and solute through membrane. 

Glomerular filtration is a passive process, where hydrostatic pressures force fluids and solute through membrane. 

As the glomerular filtrate travels through the tubules of the nephron, its composition changes. Why?

• The kidney reabsorbs useful substances (like glucose, water, ions) back into the blood.

• It can also secrete waste substances from peritubular and vasa recta capillaries into the tubules.

Why is it important to keep proteins in the plasma during filtration?

• Plasma proteins (like albumin) help maintain oncotic pressure, which keeps fluid inside blood vessels.

• If proteins are filtered out into urine, the blood loses its ability to hold fluid → this can lead to edema (swelling) and low blood volume.

• The kidney's filtration barrier (endothelium, basement membrane, and podocytes) is designed to prevent large proteins from passing through into Bowman’s space.

• __________ = protein in urine

• __________ = blood in urine

Either of these means _____________________

• Proteinuria = protein in urine

• Hematuria = blood in urine

Either of these means the filtration barrier is damaged

Why is proteinuria important?

• it is an early warning sign of kidney damage

• if untreated, could lead to chronic kidney disease, end-stage renal disease, or renal failure

The kidneys filter the body’s entire blood plasma about __________ times per day.

The kidneys filter the body’s entire blood plasma about 60 times per day.

What does filtered load measure?

The amount of substance present in Bowman’s Space per unit time.

The excretion rate (amount of substance present in urine per unit time) can be measured by the formula: _______________

Excretion Rate = U_x x V

• U → urine concentration of substance (mg/ml)

• V → urine flow rate (ml/min)

By comparing Filtered Load vs. Excretion Rate, we can determine ______________________.

By comparing Filtered Load vs. Excretion Rate, we can determine if a substance is being reabsorbed back into the blood or secreted into the urine.

The walls of both afferent arterioles (AA) and efferent arterioles (EA) contain _______________

The walls of both afferent arterioles (AA) and efferent arterioles (EA) contain vascular smooth muscle cells

The pressure pushing blood into the glomerulus is largely determined by ____________

The pressure pushing blood into the glomerulus is largely determined by MABP

_________ is a major determinant (Pushing force) of GFR

P_GC is a major determinant (pushing force) of GFR

Vasoconstriction of the AA causes….

 AA constriction → ↓ P_GC → ↓ GFR → ↑ MABP

Vasodialation of the AA causes…

AA dilation → ↑ P_GC → ↑ GFR → ↓ MABP

Vasoconstriction of EA causes…

EA constriction → ↑ P_GC → ↑ GFR

Vasodialtion of EA causes…

EA dilation → ↓ P_GC → ↓ GFR

• Increased GFR means __________________

• Decreased GFR means _________________

• Increased GFR means more fluid is filtered/pushed into Bowman’s Space

• Decreased GFR means less fluid is filtered/pushed into Bowman’s Space

_____________ pressure (MABP) pushes fluid out (filtration) of the glomerulus and ______________ pressures (Bowman’s space pressure + plasma oncotic pressure) resist filtration.

Upstream pressure (MABP) pushes fluid out (filtration) of the glomerulus and downstream pressures (Bowman’s space pressure + plasma oncotic pressure) resist filtration

What is the formula for net filtration pressure (NFP)?

NFP = P_GC – P_BS –  (π_GC – π_BS)

• P_GC –Glomerular capillary hydrostatic pressure (main force pushing fluid into Bowman’s space)

• P_BS – Hydrostatic pressure in Bowman’s space (opposes filtration)

• π_GC – Oncotic pressure of plasma proteins in glomerulus (pulls water back into blood, opposes filtration)

• π_BS – Normally ≈ 0 (since no protein should be in Bowman’s space)

What is the formula for GFR?

GFR = K_f  (P_UF)

o   K_f – Filtration coefficient (surface area × permeability of glomerular membrane)

o   P_UF –  Net filtration pressure (same as NFP)

An increase in renal artery pressure would result in ______________

increased P_GC and increased GFR

An increase in afferent arteriole resistance would result in ______________

decreased P_GC and decreased GFR

A decrease in π_GC would result in ______________________

increased GFR

An increase in P_BS would result in _______________

decreased GFR

• b/c increased backward pressure opposes filtration

• obstruction by stone or enlarged prostate

An increase in π_BS would result in _______________

increased GFR

• b/c proteins in Bowman’s space pull more fluid out of capillaries

Why is inulin clearance the gold standard for measuring GFR?

Inulin is only filtered and not handled in any other way

• Freely filtered at the glomerulus (it easily enters Bowman’s space)

• Not reabsorbed by the tubules

• Not secreted into the tubules

• Not metabolized or produced by the body

For the renal clearance of creatine, the rate of production _______________ rate of excretion

For the renal clearance of creatine, the rate of production equals rate of excretion

GFR (Clearance_Cr) is ____________ related to Plasma_Cr

GFR (Clearance_Cr) is inversely related to Plasma_Cr

Why is creatinine used to estimate GFR clinically?

o   No infusion required (unlike inulin)

o   Body makes it naturally (Stable P[Cr])

o   Easy to measure (P[Cr] & U[Cr])