RBF & GFR Flashcards
what % of cardiac output (CO) do the kidneys receive at rest
20%
(1 L/min, if CO is 5 L/min)
what % of the plasma volume that enters the kidneys is filtered
20%
what organ has the highest mass specific flow rate to any organ in the body
kidneys
blood volume leaving kidneys via renal vein = _____
blood volume entering kidneys via renal arteries
equation for mass specific flow rate
= flow rate / mass of the organ
renal mass specific flow =
400 ml / 100 g/min
GI and liver mass specific flow =
100 ml / 100 g/min
heart and brain mass specific flow =
50-70 ml / 100 g/min
skeletal muscle mass specific flow =
5 ml / 100 g/min
what is mass specific flow rate
the flow per gram of tissue
what does the high pressure of the glomerular capillaries cause
net filtration of fluid into the nephron
what does the low pressure of the peritubular capillaries cause
net reabsorption of fluid & solutes back into the blood stream
2 unique components of blood flow in the nephron
2 resistance vessels (arterioles) in series- on either side of glomerular capillaries
2 sets of capillary beds (divides labor of filtration & reabsorption between them)
how much RBF does the cortex receive, what does this do for the nephron
90-95%
maximizes flow dependent processes
what does the RBF look like in the medulla, and why
restricted RBF going into the medulla
bc of the high resistance of the descending peritubular capillaries
another name for peritubular capillaries
vasa recta capillaries
why is it important to have low RBF through the medulla
in order to produce & maintain the osmotic gradient between ISF and medullary portion of nephron
why might there be potential for hypoxic injury in the outer medulla
bc low RBF here could limit oxygen availability
3 reasons we need high cortical RBF
-to deliver enough plasma to keep high glomerular filtration rates
-to reabsorb most of the filtered water/solutes (via active transepithelial transport)
-to deliver nutrients & O2 to renal cells to support renal metabolism
what % of total body BMR (basal metabolic rate) do the kidneys use
7.5% (mostly the cortex)
what are the 2 organs (in order) with the highest mass specific O2 consumption rate (O2 consumption / per gram of tissue)
1) heart
2) kidneys
equation for RBF
RBF = delta P / R
blood flow rate entering kidneys = _____
blood flow rate exiting kidneys
(in a healthy person) initial filtrate / tubular fluid in Bowman’s space = _____, except _____
very similar composition (of inorganic ions, organic solutes) to plasma
except very little proteins and NO blood cells
3 layers of the glomerular filtration barrier
1) fenestrated endothelium of the glomerular capillaries
2) podocytes (modified epithelial cells) -> have projections called pedicels (that interdigitate- filtration slits are in between them)
3) common basement membrane (basal lamina)
what structure does each filtration slit have
a filtration diaphragm
what SMALL solutes CAN cross the glomerular filtration barrier
-almost all small solutes regardless of charge
-inorganic ions (except for divalent ions)
-AAs (oligopeptides)
-simple sugars (oligosaccharides)
-other (ex. vitamins, organic ions, urea, metabolic waste, drugs)
what LARGE solutes CAN cross the glomerular filtration barrier
-depends on both size & charge
freely filtered:
-any solute smaller than 6 kDa, or MR (molecular radius) , 1.5 nm
what LARGE solutes CANNOT cross the glomerular filtration barrier
-any solute larger than 70 kDa, or MR (molecular radius) > 3.5 nm
2 locations of fixed negative charge in the glomerular filtration barrier
-common basement membrane
-slit filtration diaphragm (between pedicels around each filtration slit)
why does the common basement membrane have a fixed negative charge
it contains heparin sulfate proteoglycans (that have a large amount of neg charge)
what is the potential risk of the glomerular filtration barrier losing its fixed negative charges
filtration of protein (proteins are usually neg charge themselves, so are usually repelled by the neg charge of the barrier)
GFR equation
GFR = k(NFP)
GFR: glomerular filtration rate
k: filtration coefficient of filtration barrier
NFP: net filtration pressure across the glomerular capillary endothelium
what happens when filtration pressures > absorptive pressures
net fluid filtration
what happens when filtration pressures = absorptive pressures
no net movement
what happens when filtration pressures < absorptive pressures
net fluid reabsorption
what are the filtration pressures (in both systemic & nephron capillary), and what do they do
P (C) = P (GC)
pi (i) = pi (BS)
pushes fluid out of capillary
what are the absorptive pressures (in both systemic & nephron capillary), and what do they do
P (i) = P (BS)
pi (C) = pi (GC)
pulls fluid into capillary
what should overall filtration look like in the peritubular capillaries
net reabsorption
what should overall filtration look like in glomerular capillaries
net filtration
why does capillary hydrostatic pressure fall when going from glomerular capillary -> to peritubular capillary
bc we’re going through efferent arteriole (a high resistance vesicle)
what is the primary driving force of filtration rate
glomerular capillary hydrostatic pressure
what factors affect glomerular capillary hydrostatic pressure
-aortic/renal artery pressure (MAP)
-resistance (diameter) of afferent arteriole
-resistance (diameter) of efferent arteriole
increase in resistance (decrease in diameter) of afferent arteriole OR efferent arteriole = _____ RBF
decreases RBF
equation for RBF
RBF = P / R
P: pressure
R: resistance
increase in resistance of ONLY afferent arteriole = _____ RBF bc _____ & _____ GFR bc _____
decreases RBF bc blood flow thru kidneys is less
decreases GFR bc hydrostatic pressure of glomerular capillary decreases
increase in resistance of ONLY efferent arteriole = _____ RBF bc _____ & _____ GFR bc _____
decreases RBF bc blood flow thru kidneys is less
increases GFR bc hydrostatic pressure of glomerular capillary increases
increase in resistance of BOTH afferent & efferent arterioles = _____ RBF & _____ GFR
decreases RBF bc blood flow thru kidneys is less
possibly unchanged GFR bc hydrostatic glomerular capillary pressure may be unchanged (same flow into & out of GC)
what happens to GFR if efferent arteriole has very high resistance & remains constricted way longer than normal
even tho GFR initially increases, if efferent arteriole remains constricted, GFR begins to decrease after a while bc decreasing RBF convinces it to
how does RBF remain the same as pressure (P) increases
resistance (R) must also increase
RBF = P / R
what is primarily responsible for RBF remaining constant
intrinsic regulation of afferent arteriole resistance (will increase when P increases, to keep RBF the same [efferent arteriole resistance doesn’t change])
in addition to RBF, what else stays relatively constant over a wide range of pressures
GFR
2 mechanisms of autoregulation of afferent arteriole resistance
arteriolar myogenic regulation
tubuloglomerular feedback (TGF)
arteriolar myogenic regulation autoregulates afferent arteriole resistance via _____
stretch induced vascular smooth muscle contraction
tubuloglomerular feedback autoregulates afferent arteriole resistance via _____
paracrine secretions by the macula densa
what is the juxta-glomerular apparatus (JGA) comprised of
-macula densa (modified TALH ~or~ early distal tubule cells)
-granular/JG cells (modified smooth muscle cells)
-mesangial cells
where is the macula densa located
in the ascending limb of the LoH- where it goes up & in between the afferent and efferent arterioles- the modified TALH/early distal tubule cells are against the afferent & efferent arterioles
tubuloglomerular feedback (TGF) mechanism if increase in blood flow occurs (but opposite can occur)
increase in blood flow = increase in GFR
->
increases fluid flow thru tubule (less time to reabsorb Na+/Cl- from fluid)
->
increases flow past macula densa (& this fluid has more NaCl than usual)
->
macula densa has NKCC that can reabsorb NaCl
->
bc more NaCl is being absorbed = a paracrine signal molecule (adenosine in the form of ATP) is secreted from macula densa cells into ISF
->
adenosine goes to JG cells & signals for afferent arterioles to constrict
->
increases resistance in afferent arterioles
->
decreases hydrostatic pressure in GC
->
decreases GFR back down to normal
range of renal/arterial pressure that autoregulation works at
80-180 mmHg
2 categories of how RBF is regulated
1) local, intrinsic control
-myogenic/TGF autoregulation
-local, paracrine agents
2) extrinsic, neurohormonal regulation
general definition of extrinsic control of RBF
complex interaction between opposing neurohormonal systems ->
impacts degree of vasoconstriction of afferent and/or efferent arterioles
what are the 2 systems of extrinsic control of RBF
vasoconstrictor system (salt-retaining)
vasodilator system (salt-excreting)
extrinsic regulation of RBF plays a major role in _____
regulating BP, salt & water homeostasis
what does the vasoconstrictor system do
(salt-retaining)
protects against hypovolemia & hypotension
what does the vasodilator system do
(salt-excreting)
protects against hypervolemia & hypertension
filtered load equation (how much was filtered across the glomerulus)
quantity excreted equation (how much was excreted in the urine)
(= the numerator of the clearance equation)
clearance equation
filtration fraction (FF) equation (& equation using markers)
FF = GFR / RPF
FF = (creatinine clearance) / (PAH clearance)
FF: %
what does filtration fraction mean
fraction of plasma entering glomerular capillaries that is filtered into tubule
what is “clearance”
the rate that a substance is removed (“cleared”) from the plasma
define “renal clearance” in general
the rate that a substance is removed (“cleared”) from the plasma AND excreted in the urine
define “renal clearance” specifically
the volume of plasma that is completely cleared of a solute by the kidneys per unit time
(ml/min)
what does clearance tell you about the solute
if it is reabsorbed or secreted
2 markers whose clearance can tell you GFR
inulin
creatinine
1 marker whose clearance can tell you RPF (renal plasma flow rate)
PAH (organic anion)
if clearance of solute < clearance of inulin/creatinine, then _____ occurs
net reabsorption
if clearance of solute > clearance of inulin/creatinine, then _____ occurs
net secretion
if quantity filtered = quantity excreted, then that solute’s clearance _____
estimates GFR
what is a GFR marker
a solute whose clearance is an estimate of GFR
4 requirements for a solute to be a GFR marker
-must be freely filtered (TF/P ratio in bowman’s capsule = 1)
-cannot be reabsorbed / secreted by tubules
-must be physiologically inert (non-toxic & has no effect on renal function)
-cannot undergo extrarenal elimination
if GFR marker requirements are met: quantity of solute in urine (per unit time) = _____
quantity of solute filtered by glomerulus (per unit time)
what is inulin
polymer of fructose
gold standard for measuring GFR (injected into body)
why is inulin not actually useful clinically
-requires constant IV infusion
-chemical analysis is complicated
-not readily available in US
exogenous GFR markers
inulin
iothalamate, iohexol
radiolabeled markers (low quantity of a solute labeled w radioactive molecule)
creatinine (most commonly used)
advantage of iothalamate, iohexol
they are renal contrast media (can additionally see kidneys well on imaging)
disadvantage of iothalamate, iohexol
may be nephrotoxic
advantage of radiolabeled markers
uses low quantity of solute that may be toxic at higher quantities
disadvantage of radiolabeled markers
expensive & needs special equipment
6 advantages of creatinine as GFR marker
-produced by skeletal muscle
-[plasma creatinine] usually at steady state
-only need blood & urine sample
-cheap
-reliable
-easy to use in clinic
disadvantage of creatinine as GFR marker
may be influenced by sex, muscle disease, pt diet (consuming animal muscle often vs vegan)
what makes creatinine an imperfect GFR marker, what is the consequence of this, and why does it work out anyway
is secreted into the nephron a little
->
creatinine clearance may overestimate GFR ~10-20%
->
but works out bc colorimetric assays used tend to underestimate concentration
->
so creatinine clearance usually = inulin clearance in the end
why is PAH a good RPF (renal plasma flow) marker, & what can be the general statement then
it is 90% cleared from the blood
PAH clearance = RPF
equation relating RPF and RBF
RPF = RBF x (1 - Hct)
ex.
if Hct = 0.40 (Hct is 40% of blood volume),
then 60% of blood volume = RPF
