Questions: Glomerular Filtration and Filtration Rate Regulation

Question 1

A drug that moderately constricts only the efferent arteriole is administered. What effect does this have on GFR, and why?

• A. GFR decreases because the drug reduces total blood flow through the glomerulus
• B. GFR increases because outflow resistance raises glomerular capillary hydrostatic pressure
• C. GFR is unchanged because the kidney's autoregulation fully compensates
• D. GFR decreases because Bowman's capsule pressure rises to match the elevated capillary pressure

Answer: (B)

Moderate efferent arteriole constriction impedes outflow while blood still enters through the afferent arteriole, backing up pressure in the glomerular capillaries. This elevated hydrostatic pressure increases the net filtration pressure and raises GFR. The common misconception is that constricting any vessel downstream must reduce GFR — but the unique dual-arteriole architecture means efferent resistance specifically raises intraglomerular pressure rather than simply cutting flow. (Severe constriction eventually reduces GFR by cutting total flow, but moderate constriction increases it.)

Question 2

What makes the glomerular capillary bed structurally unique compared to most systemic capillary beds?

• A. It is surrounded by a porous membrane that lacks the standard three-layer filtration barrier
• B. It is positioned between two arterioles — the afferent and efferent — rather than between an arteriole and a venule
• C. It operates at unusually low hydrostatic pressure to prevent excessive protein loss
• D. It lacks oncotic pressure because plasma proteins freely cross the filtration barrier

Answer: (B)

In most capillary beds, blood flows from arteriole → capillary → venule. The glomerulus is sandwiched between two arterioles: the afferent (inflow) and efferent (outflow). This architecture allows the kidney to independently regulate pressure within the glomerular capillaries by adjusting resistance at either end, enabling fine-tuned control of GFR that would be impossible with a single downstream venule.

Question 3

Constricting the afferent arteriole increases GFR by raising glomerular capillary hydrostatic pressure.

• T. True
• F. False

Answer: False

Afferent arteriole constriction reduces blood flow into the glomerulus, lowering glomerular capillary hydrostatic pressure and therefore decreasing GFR — the opposite effect. This is what happens during sympathetic activation in severe hemorrhage: the body diverts blood away from the kidneys by constricting the afferent arteriole. Efferent constriction (not afferent) is what raises intraglomerular pressure.

Question 4

Albumin is nearly absent from the glomerular filtrate partly because the negatively charged proteoglycans in the glomerular basement membrane repel it, not just because of albumin's large molecular size.

• T. True
• F. False

Answer: True

The glomerular filtration barrier uses two selection principles: size and charge. The glomerular basement membrane contains negatively charged proteoglycans that electrostatically repel negatively charged molecules like albumin. In conditions that damage this charge barrier (e.g., minimal change disease), significant albumin appears in the urine even though albumin's size hasn't changed. Both the physical size filter and the electrostatic charge barrier must be intact for effective filtration.

Question 5

During severe hemorrhage, GFR falls sharply. Using the concept of arteriolar resistance, explain the two mechanisms responsible for this drop.

Model answer: First, sympathetic nervous system activation causes afferent arteriole constriction, reducing blood flow into the glomerulus and lowering glomerular capillary hydrostatic pressure — directly reducing net filtration pressure and GFR. Second, systemic blood pressure itself falls due to hemorrhage, which also reduces the pressure driving blood into the glomerulus. Together, these two mechanisms — neural afferent constriction and reduced perfusion pressure — drastically lower GFR, conserving what little fluid remains in circulation.

Understanding this requires seeing GFR as directly dependent on glomerular capillary hydrostatic pressure, which is itself governed by (1) the pressure of blood arriving from the systemic circulation and (2) the resistance of the afferent arteriole regulating how much of that pressure reaches the glomerulus. Sympathetic activation is an active protective mechanism — it deliberately sacrifices renal filtration to preserve blood pressure in vital organs.