The Glomerulus: Structure & Function

How is urea filtered in the glomerulus?

Glucose: also freely filtered but is completely resorbed; clearance rate is 0; not removed from plasma through the kidney Urea: partially resorbed (65 mL/min); another possible measure for kidney function

Describe the endothelial cell layer of the glomerulus

Single layer of endothelial cells lining glomerular capillaries; contain fenestrations; restrict passage of RBC

How do AGII & noradrenaline affect GFR?

Vasoconstriction = reduced GFR Reduced blood flow = reduced blood volume / min = reduced GFR

What is GFR?

Volume of fluid filtered from glomeruli into Bowman's capsule per unit time Extremely tightly regulated

What three forces contribute to GFR?

Hydrostatic pressure: pushes fluid out of capillaries due to flow rate of blood; favors filtration Oncotic pressure: osmotic pressure caused by proteins; opposes filtration Net filtration pressure: from capillary lumen --> capsular space

What is plasma clearance & what is it used for?

Clearance = volume of plasma from which a substance is completely removed by the kidney in a given amt of time Measuring renal clearance allows us to analyze kidney activity

What drugs are used to block vasodilators acting on GFR?

NSAIDS; block PGE2

What is normal GFR?

125 mL/min

How many mL of plasma enter the glomerulus perminute?

625 mL

What are the three layers of the glomerular filter?

1. Endothelial cells 2. Glomerular basement membrane 3. Podocytes

How does ACE affect GFR?

ACE constricts afferent arteriole which causes a reduced blood flow to the glomerulus Reduced blood flow = reduced blood volume / min = reduced GFR

What is autoregulation & what two methods are used in the kidney?

Ability of the kidney to maintain constant pressure & GFR despite systemic BP changing

GFR depends on the pressure difference between which two vessels?

Afferent & efferent arterioles; together they affect hydrostatic pressure of glomerular capillaries

Describe tubuloglomerular feedback as a means of autoregulation of the kidney

Alteration in tubular flow (changes in [Na] & [Cl] in distal tubule) sensed by macular densa cells of the juxtaglomerular apparatus Releases signals to alter GFR appropriately: Low [Na] & [Cl] = too low GFR bc more [Na] & [Cl] absorbed earlier in system = release signals to raise GFR (PGE2) High [Na] & [Cl] = too high GFR bc not as much [Na] & [Cl] absorbed earlier in system = release signals to lower GFR (AGII)

How does hydrostatic BP affect GFR?

BP w/in glomerular capillaries; main determinant of GFR Higher BF = higher BP = higher hydrostatic pressure (fluid pushing more on BV wall)

How does an ACE inhibitor affect GFR?

Body will try to combat low GFR by increasing BP ACE inhibitors will block ACE to keep BP low, TF used to combat high BP

Describe how creatinine clearance can help determine GFR

Breakdown product of creatinine phosphate (found in muscle) Usually steady-state concentration in plasma; freely filtered by glomerulus; tends to overestimate GFR by 10-20% Easier/quicker to measure creatinine clearance as already steady-state Limitations: endogenous substance so can be altered; less precise than inulin

Describe the glomerular basement membrane

Btw endothelium & visceral layer; main filtration barrier

How do vasodilators (PGE2, NO) affect GFR?

Dilation of afferent vessels = more blood flow = more blood volume / min More BV/min = increased GFR

Describe the components of filtrate in Bowman's capsule

Filtrate in Bowman's capsule is essentially protein-free Contains all substances present in plasma in appx same concentration; [filtrate] = [plasma] Exceptions: some low-MW substances & those bound to protein (FA, Ca, etc)

What is the significance of the filtrate/plasma ratio?

Filtration properties of glomerular filter can be determined by filtrate/plasma concentration ratio F/P ratio of <1 means substances are being withheld from filtration; [plasma] > [filtrate]

How is glucose filtered in the glomerulus?

Glucose: also freely filtered but is completely resorbed; clearance rate is 0; not removed from plasma through the kidney

What two forces determine capillary filtration?

Hydrostatic pressure: pushes fluid out of capillaries due to flow rate of blood; favors filtration Oncotic pressure: osmotic pressure caused by proteins; opposes filtration

How is inulin clearance used to determine filtration status?

If a substance (ex. Inulin, NOT insulin) is freely filtered by glomerulus & not resorbed/secreted, its clearance rate is equal to GFR (125mL/min) TF we can determine whether kidneys are filtering properly by measuring inulin clearance:

How do mesangial cells affect GFR?

Irregular shaped cells lying btw glomerular capillaries (above) Capable of contraction in response to different hormonal mediators; equivalent to vascular smooth muscle Intraglomerular: some phagocytic activity Extraglomerular: found @ vascular poles; part of juxtaglomerular apparatus

How does renal blood flow affect GFR?

Pressure in renal artery ~ systemic BP Most vascular resistance in the kidneys derives from changing diameter of interlobular arteries & afferent/efferent arterioles Resistance controlled by: sympathetic NS, hormones, autoregulation

What is proteinuria?

Proteinuria: loss of negative charge on the barrier (or change in barrier structure) allowing passage of abnormal levels of protein into the urine

What is the equation for renal blood flow?

RBF (Q) = afferent-efferent arteriolar pressure (DP) / Resistance (R)

What is renal plasma flow & what is it used for?

Renal plasma flow: volume of plasma delivered to kidney per unit time Some fluid leaves kidneys as plasma or urine For urine, must be either filtered & not absorped OR not filtered but secreted into capillaries; either way will end up in collecting duct & be excreted

What are podocytes & what is there role in the glomerulus?

Single layer of epithelial cells lining Bowman's capsule; phagocytosis of macromolecules & restricts passage of medium-sized proteins

The filtration barrier in the glomerulus separates solutes based on ______

Size & charge Size: nothing over 70,000kDa will pass through Charge: filter is negatively charged; cation > anion filtration

Describe myogenic tone as a means of autoregulation of the kidney

Smooth muscle sensors in afferent arteriole; stretch when pressure is too high Afferent arteriole constricts in response to stretch, increasing afferent arteriole resistance