Glomerular Filtration

General

kidneys are 0.5%-1% of body weight; receive 20%-25% of CO; RBF = 1.6 L/min

allows for rapid regulation of body fluids

RPF (renal plasma flow) = 650 mL/min

GFR (glomerular filtration rate) = 125 mL/min (180 L/day)

filtration fraction = GFR/RPF = 0.20

RBF = RPF / (1 - hematocrit)

Ultrafiltration

plasma water and non-protein constituents are filtered into Bowman’s space; colloids and RBC not

glomerular basement membrane is permselective; ultrafiltrate is almost protein free

GFR is sum of all SNGFR

GFR is the best index of renal function: decline means progression of disease; rise means recovery

Structural Basis of Glomerular Filtration

filtration is based on size and charge

size is thought to be based on pores (don’t confuse with channels) in the basement membrane

<7,000 kDa freely filtered; >70,000 kDa not filtered

charge based on anions in glomerulus (glycosialoproteins) repel neg charged particles (i.e. most proteins)

dextran experiments

current model for filtration: fenestrae in glom cap endothelium; glomerular BM; slit diaphragms; slits between podocyte foot processes

proteinuria: hallmark of renal disease; results from breakdown of charge and size selectivity

Determinants of GFR

Starlings forces: K_f = net permeability (porosity x SA); P = hydraulic pressure; P = oncotic pressure

filtrate has few proteins, P _bs ~ 0; equation reduces to: GFR = K_f(P_gc - P_bs - P _gc)

factors that affect these terms in handout table p. 8

glomerular caps are much less permeable to proteins than systemic caps

K_f is 100x higher in renal caps (so very selective filtration)

transcapillary pressure is 2-3x higher in renal caps (filtration mostly driven by hydrostatic pressure)

Hyperfiltration in Glomerular Disease

reduction in filtration in renal disease is mostly due to drop in K_f

usually from loss of surface area (i.e. loss of nephrons)

increase in P_gc and RPF through afferent arteriole leads to hyperfiltration in remaining nephrons

this, in turn, leads to further nephron damage, and so on

in primary glomerular disease have glomerular hypertrophy to compensate by increasing SA

Regulation of GFR

arterial resistance determined by: neurohormonal (myogenic) control; tubularglomerular feedback; ANGII; norepi, etc

afferent constriction: decreases GFR; efferent constriction: increases GFR

autoregulation: increase in pressure causes vasoconstriction (afferent)

helps maintain constant RBF and GFR

balance between: 1) Ý press Þ Ý GFR; 2) (afferent) vasoconstriction Þ ß GFR

ANGII preferentially increases resistance at efferent arteriole in states of hypotension (ß blood pressure)

TGF (tubuloglomerular feedback): maintains GFR and keeps distal flow constant (distal reabsorption easily overwhelmed)

decreased delivery of NaCl to macula densa causes efferent constriction Þ increase GFR and restore flow via renin

if RBF or RBP too high, TGF can initiate afferent constrict when increased flow sensed in MD via adenosine

myogenic control

epi causes afferent and efferent constriction; combined with ANGII Þ maintained GFR with decreased RBF

vasodilatory prostaglandins (secretion stim by ANGII) dampen effects of ANGII and sympathetic nervous system

PGE₂ and PGI₂ are afferent vasodilators

Importance of Neurohormonal Regulation of GFR in Renal Disease

non-steroidal anti-inflamitory drugs (NSAIDS): inhibit prostaglandin synth and could be dangerous to patients who are volume depleted because the effects of ANGII are not dampened

in this case, NSAIDS could cause acute renal failure