Renal 3- Glomerular Filtration, Renal blood flow, and their control Flashcards
what is GFR (number)
125 ml/min or 180 L/day
entire plasma volume is filtered every ____
24 minutes
how does GFR occur
via bulk flow
what is GFR selective for
cells, proteins, Ca2+, fatty acids and other protein bound substances
what is filtration fraction
GFR/RPF
what does filtration fraction average
20% of renal plasma flow
what does the renal corpuscle contain
-bowmans capsule -parietal and visceral layers
-glomerular capillaries - glomerulus
- bowmans space
where is protein free fluid filtered into in glomerular filtration
filtered out of glomerulus into bowmans space
where does protein free fluid flow into
proximal tubule
what is blood in glomerular capillaries separated from bowmans space by
a filtration barrier
what are the 3 layers of the glomerulus
- capillary endothelium: fenestrated
- basal lamina: basement membrane
- podocytes: visceral layer of bowmans capsule
what are podocytes and what do they do
- foot processes that cover outside of basal lamina
- creates filtration slits
what are mesangial cells and where are they found
- modified smooth muscle cells
- surround glomerular capillary loops
what do mesiangial cells do
- modify size of filtration slits and alter rate of filtrate production
- not a part of filtration barrier
what do substances have to be small enough to fit through to be filtered
filtration pores
is protein lost in excretion
no
what are the determinants of the ability of a solute to penetrate the glomerular membrane
-molecular size (small molecules filter better than large
- ionic charge (cations filter better than anions)
- proteins are both large and negatively charged and do not filter well
in minimal change nephropathy ____
-loss of negative charge on GBM
- proteins filtered through GBM
- proteinuria
what is the formula for GFR involving starlings forces
GFR = Kf x NFP
what is capillary filtration coefficient (Kf)
product of the permeability and surface area of the capillaries
what is NFP
balance of hydrostatic and colloid osmotic forces acting across the capillary membrane
what starlings forces would cause GFR to be high
high hydrostatic pressure and high Kf
what is NFP (number)
10mmHg, 125 ml/min or 180 L/day
describe the glomerular capillary filtration coefficient Kf
-400x higher than any other capillary bed
- normally not highly variable
- alterations in Kf not used to regulate GFR
how can diseases lower Kf
- thickened basement membrane: hypertension, DM
- decreased capillary surface area: glomerulonephritis
what are the two hydrostatic pressures that regulate GFR
- glomerular
-bowmans capsule
what is the primary control point for GFR
glomerular hydrostatic pressure
which hydrostatic pressure is a physiological controller of GFR: glomerular or bowmans
glomerular
what are the factors that influence glomerular hydrostatic pressure (Pg)
-arterial pressure (effect is buffered by autoregulation)
- afferent arteriolar resistance
-efferent arteriolar resistance
what diseases can affect GFR via PB (hydrostatic pressure of Bowmans capsule)
-tubular obstruction (stones, tubular necrosis)
-urinary tract obstruction (prostate hypertrophy/cancer)
what does glomerular capillary colloid osmotic pressure increase along
length of glomerular capillary
-affected by filtration fraction
what does glomerular capillary colloid osmotic pressure oppose
hydrostatic pressure
what happens to GFR along the length of the capillary
decreases
-factors that affect PiG
what is piG proportional to
[protein] plasma and FF (fraction of blood flow filtered in nephron)
how can hydrostatic pressure in glomerular capillaries be altered
by altering the resistance of the afferent and efferent arterioles leading to changes in GFR
what happens to PG and GFR when you constrict the efferent arteriole
PG: decreases
GFR: decreases
what happens to PG and GFR when you dilate the efferent arteriole
PG: decrease
GFR: decrease
what happens to PG and GFR when you constrict the efferent arteriole
PG: increase
GFR: increase
what happens to PG and GFR when you dilate the afferent arteriole
PG: increase
GFR: increase
an increase in efferent arteriolar resistance causes an increase in GFR only until a certain point where GFR then decreases. why?
due to increased [plasma protein] caused by increased filtration fraction
what are factors than can decrease GFR directly and what are the physiologic causes of those
-decreased Kf: renal disease, DM, HTN
- increased PB: urinary tract obstruction
- increased piG; increased [proteins]plasma, dehydration
-decreased Pg
what are factors that decrease GFR by decreasing PG and what are the physiological causes of those
- decreased MAP: low arterial pressure
- decreased RE: low ANG II
-increased RA: increased sympathetic activity, vasoconstrictor hormones
what is the formula for renal blood flow
RBF = (Pa-Pv)/total renal vascular resistance
how do kidneys tightly control RBF
renal autoregulation
what is vascular resistance in renal blood flow regulated by
factors acting on afferent and/or efferent arterioles (70% of total intrarenal resistance)
what percentage of blood flow into medulla makes up total RBF
less than 10%
what does a very low flow in vasa recta contribute to
concentrated urine
what does high RBF reflect in terms of energy
high energy cost of active transport
what are the primary active transporters in renal blood flow
- Na+ K+ ATPase
- H+ ATPase
- H+ K+ ATPase
- Ca2+ ATPase
what are the 3 levels of control of RBF
-autoregulation
- local control
-systemic control
what does autoregulation do
prevents moment to moment changes in GFR
what is the function of myogenic autoregulation
keeps RBF and GFR relatively constant in spite of changes in MAP
what is myogenic autoregulation
used in autoregulation
- reflex vessel constriction in response to increased MAP
- intrinsic to blood vessels
what is a transient drop in GFR and RBF as a result in a decrease in renal artery pressure followed by
vasodilation
what is a transient increase in GFR and RBF as a result of an increase in renal artery pressure followed by
vasoconstriction
what is the function of tubuloglomerular feedback (TGF)
-helps ensure a nearly constant delivery of Na+ and Cl- to the distal nephron
- prevents spurious fluctuations in renal excretion
what does the JGA do
mediates the TGF response
what is the JGA composed of
-juxtaglomerular cells (granular cells)
-macula densa cells in the wall of the thick ascending loop of henle
where are JG cells located and what do they do
-primarily in walls of afferent arterioles
-secrete renin
what do macula densa cells do
sense [Na+] and [Cl-] in filtrate
what is the mechanism of action of JGA
decreased GFR -> decrease rate of filtrate flow in nephron -> increased Na+/Cl- reabsorption -> decreased Na+/Cl- delivery to MD -> sensed by MD -> signals sent to JG cells -> increased renin secretion and other paracrines -> increased ANGII production and other paracrines -> increased RE and decreased RA -> increased PG -> increased GFR
what are the stimuli for renin release
-low BP
- low RBF
- low NaCl delivery to macula densa
describe the TGF response
-low arterial pressure -> low glomerular hydrostatic pressure -> low GFR -> macula densa ->decreased RA and increased renin and ANGII to increase RE
what feedback effect do increased RE and decreased RA have on the TGF repsonse
negative feedback on the glomerular hydrostatic pressure
what are the vasoconstrictors in local control
-endothelin
- dopamine in high concentrations
what are the vasodilators in local control
-prostaglandins
- NO
- bradykinin
-dopamine in low concentrations
what is involved in sympathetic control of RBF and are they vasoconstrictors or dilators
-sympathetic NS (vasoconstrictor)
- epinephrine (vasoconstrictor)
- renin-angiotensin system (vasoconstrictor)
- ANP (vasodilates afferent and vasoconstricts efferent arterioles)
what role does SNS and EPI play in regulation RBF in normal state
minor role
when does SNS activation alter RBF
stress such as blood loss, cardiac events
what does NE/E do to RA, RE, RBF, and GFR
RA: increase
RE: increase
RBF: decrease
GFR: decrease
what does endothelin do to RA, RE, RBF, and GFR
RA: increase
RE: increase
RBF: decrease
GFR: decrease
what does angiotensin II do to RA, RE, RBF, and GFR
- mainly just increases RE
- RBF: decrease
-GFR: increase
what does ANP do to RA, RE, RBF, and GFR
RA:decrease
RE: increase
RBF: increase
GFR: increase
what does PGE2 and PGI2 do to RA, RE, RBF, and GFR
RA: decrease
RBF: increase
GFR: increase
what does bradykinin do to RA, RE, RBF, and GFR
RA: decrease
RBF: increase
GFR: increase
what does NO do to RA, RE, RBF and GFR
RA: decrease
RE: decrease
RBF: increase
GFR: increase
what are other factors that increase GFR and RBF
high protein diet
high blood glucose levels
what is the mechanism of protein ingestion
-increased amino acids -> increased PCT amino acid reabsorption ->PCT NaCl reabsorption -> decreased macula densa NaCl -> decreased afferent arteriolar resistance -> high GFR which does negative feedback on macula densa
what is the filtered load (Fx) of a substance and how is it calculated
-rate at which substances enter the nephron
- Fx= GFR ([X] plasma)
what is the excretion rate of a substance and how is it calculated
-rate at which substances are excreted
-Ex = (Uv)([X]urine) where Uv = urine flow rate
what is the clearance rate of a substance and how is it calculated
- determines the volume of blood cleared of a substance in a given amount of time
-Clx = Ex/[X]plasma
the clearance rate of what 2 substances are used as an index of GFR
inulin and creatinine
the clearance rate of what substance is used as an index of RBF
PAH
