0804 - Glomerular Filtration and its Determinants

Question 1

Outline the physiologically relevant parts of renal anatomy

Answer 1

Vascular - Afferent Arteriole ->Glomerulus -> efferent arteriole->peritubular capillaries Bowman’s Capsule -> Proximal tubule ->Loop of Henle (TDL, tDL, tAL, TAL), distal tubule and juxtaglomerular apparatus -> cortical connecting tubule -> medullary connecting tubule -> collecting duct.

Question 2

Discuss the significance of the micropuncture technique in studying renal function

Answer 2

Allows access to renal ultrafiltrate. Oil drop enters the PT, hindering passage of fluid, and allowing it to run up the micropipette instead.

Question 3

Explain what makes up the glomerular filter and its properties

Answer 3

It’s an ultrafilter - water and smaller molecules pass through, while cells, colloids, and larger molecules are retained within the vasculature. Driven by pressure difference between glomerular capillaries and Bowman’s Space. Consists of 3 layers: Endothelial fenestrations between capillary cells. Matrix of basal membrane consisting of collagen and proteins Podocytes - fine filter with slits that can vary in size. Negatively-charged peptides are retained (relatively) as they are much less filterable than positively charged ones of an equivalent size (limit 69,000D)..

Question 4

Demonstrate why and how the following factors determine filtration:

Answer 4

P(Eff)=P(Cap)-π(Colosm)-P(Interst). As πColosm increases along capillary, PEff drops to 0 quite quickly - filtration can thus be increased by increasing PCap. P(Cap) - Primary driving force for filtration (around 60torr). Hydrostatic pressure in capillary, produced by left ventricle. Stays constant along capillary. P(Interst) - Pressure within the Bowman’s capsule that needs to be overcome - effectively pushing back on capillary. Stays constant along capillary. π(Colosm) - Osmotic pressure within the capillary (plasma proteins, Na etc) that wants to draw water back into the capillary. However, as water without colloids is sucked out, this rises along the capillary.

Question 5

Identify mechanisms involved in constance of perfusion (autoregulation)

Answer 5

2 ways:

• Change in MAPr (Myogenic, Bayliss) - tendency of smooth muscle to contract when stretched (TRPC channels).
• Changes in [NaCl] via juxtaglomerular apparatus - Mediators not clear, but detects [NaCl] in distal tubule (macula densa cells). If too high, constricts afferent arteriole to increase resistance and drop individual GFR to appropriate level if too low, relaxes (NO?). Ensures all glomeruli are in appropriate range. Juxtaglomerular apparatus is where distal tubule contacts arterioles.

Question 6

Discuss how GFR can be regulated independent of RBF

Answer 6

PCap changed by dilation and constriction of afferent and efferent arterioles via smooth muscle tone.

Question 7

Recognise VSMC mechanisms resulting in renal vasomotion

Answer 7

Constrictors

Sympathetic (via α1)

Angiotensin II (via AT1 receptor)

Endothelin

Adenosine (paradoxical)

Dilators

Prostaglandins (PGl2, PGE2)

NO from endothelia

Bradykinin

Dopamine

Angiotensin II (via AT2 receptor)

Increased cGMP leading to increased Ik