Glomerular Filtration

The filtration barrier is freely permeable to...

*Freely permeable* to water & crystalloids - Small solutes like electrolytes, AA's, monosaccharides - No hindrance to molecules *< 7k Da* Freely filtered molecules have a concentration ratio of 1:1 in tubular fluid in Bowman's space and in plasma *TFx / Px = 1*

Compare GFR and RBF

*GFR* = glomerular filtration rate ~ 125 ml/min or 180 L/day - Recall 20% of plasma that travels to kidney is filtered in glomerulus 20% of RPF (renal plasma flow) = 125 ml/min - Plasma ~ 55% blood volume - Large b/c of high hydraulic permeability of glomerular capillaries *RBF* = renal blood flow 1200 ml/min - Far exceeds metabolic needs

Define glomerular filtration

*Glomerular filtration* - Passive, non-selective process in which hydrostatic pressure forces fluids through the glomerulus

How does increased P,RA affect GFR

*Increased P,RA* --> Increased P,GC (increased afferent P,GC) --> Increased NFP --> Increased GFR Top picture

How does increased R,a affect GFR

*Increased R,a* (afferent arteriole resistance) --> decreased P,GC (decreased afferent P,GC) --> decreased NFP --> decreased GFR Bottom picture

How does increased R,e affect GFR

*Increased R,e* (efferent arteriole resistance) --> increased P,GC (decreased efferent P,GC) --> increased NFP --> increased GFR Highest GFR of all 3 scenarios

How does insulin-dependent DM affect glomerular filtration?

*Insulin-dependent DM* - Loss of charge barrier - Permeable to some proteins - Why you see albumin in urine

How is net filtration pressure (NFP) determined?

*NFP = ( P,GC + pi,BC ) - ( P,BC + pi,GC )* Net = Filtration - No filtration - Recall pi,BC = 0 so... NFP = P,GC - ( P,BC + pi,GC ) NFP = 24 mmHg at afferent end NFP = 10 mmHg at efferent end

Regulation of K,f

*Regulation of K,f* - Controlled physiologically by nerves & hormones - Contraction of *mesangial cells* reduce SA for exchange --> reduces K,f & ultimately GFR - Diseases that *thicken filtration barrier* reduce SA by destroying capillaries --> reduces K,f & ultimately GFR

Filtration barrier is *relatively impermeable* to...

*Relatively impermeable* to small molecules bound to proteins, 60% of plasma [Ca2+] (unbound to proteins), steroids, & peptides

What does the size barrier filter out?

*Size barrier* (7+ kDa) - In endothelial fenestrations, prevents RBC's and platelets from passing - In basement membrane, macromolecules (ie. proteins) are too large to traverse through intertwined collagen, glycoproteins, & mucopolysaccharides - In podocytes, macromolecules trapped by glycosialoproteins that coat podocytes To a small degree, shape of molecule also determines degree of filtration

The filtration barrier totally excludes...

*Totally excludes* cells, platelets, proteins > 7k Da, almost all Hb and albumin

What must the filtrate travel through before entering Bowman's space? (aka structure of filtration barrier)

1) *Endothelial fenestrae* 2) *Basement membrane* 3) *Slits* b/t podocytes 2 components of barrier: 1) Size barrier 2) Charger barrier Barrier determines filtrate composition

GFR or SNGFR (single nephron) is dependent on what 3 factors?

1) *Pressures* - GFR is directly proportional to net filtration pressure (NFP) - Starling forces govern movement of fluids across any capillary bed & determines GFR 2) *Hydraulic permeability* of filtration barrier *to water* - Ex. # aquapores per unit of SA - GFR is directly proportional to hydraulic permeability (high) 3) *SA for exchange* - GFR is directly proportional to area for exchange - Large b/c of convoluted glomerular capillaries in contact w/ Bowman's capsule *GFR = NFP x K,f* - Where K,f = filtration coefficient ; hydraulic permeability x SA

What 2 forces oppose filtration?

1) Hydrostatic P in Bowman's capsule *P,BC* ~ 15 mmHg - Not physiologically regulated BUT can increase if fluid flow is blocked (ex. kdiney stone in ureter) --> decrease NFP & GFR - Provides driving pressure for flow of fluid down nephron 2) Oncotic pressure of plasma in glomerular capillary *pi,GC* - Main force that opposes filtration ( ~21 mmHg) - Depends on oncotic pressure of arterial blood (regulated by factors that affect arterial blood) ~ 21 mmHg at afferent end ~ 33 mmHg at efferent end (increased b/c protein-free fluid is removed from capillaries via filtration, protein conc gradient of glomerular cap plasma increases)

What 2 forces favor filtration from glomerulus into Bowman's space?

1) Hydrostatic pressure in glomerular capillary (*P,GC*) - Main driving force for filtration - Physiologically regulated by changing R of afferent & efferent arteriole ~ 60 mmHg at afferent end of glomerular capillaries ~ 58 mmHg at efferent end (due to R) 2) Oncotic pressure in Bowman's capsule (*pi,BC*) - Oncotic P = osmotic P caused by colloids (mainly albumin) - Water flows from regions of high oncotic P to low - Glomerular filtrate is essentially protein-free so *pi,BC ~ 0 mmHg*

GFR regulation

Factors that can change GFR include... 1) *P,GC* - Highest influencing factor - Dependent on renal arterial pressure (P,RA), afferent arteriole R (R,a), and efferent arteriole R (R,e) - Regulated by nerves & hormones

What does the charge barrier filter out?

Molecules that form basement membrane and coats podocytes are *negatively charged* - Repels any other negatively charged molecules (ie. albumin at phys. pH)

What are the variables that can be influenced?

P,BC pi,GC P,GC K,f

What factors regulate pi,GC

Since pi,GC depends on oncotic P of arterial blood, factors that affect oncotic P of arterial blood affect pi,GC At very beginning of glomerular capillaries, pi,GC = pi, arterial plasma - Before any filtration Liver disease can cause *hypoalbuminemia* - Reduces pi, arterial plasma (and pi,GC) & raises NFP and GFR