Glomerular Filtration Flashcards
What are indicators of end-stage renal disease? (2)
- really low GFR
- high protein composition in urine
What is glomerular filtration?
filtration of fluid into Bowman’s space from glomerular capillary tuft (blood)
What is filtrate (ultrafiltrate)?
filtered fluid composed of H2O and electrolytes, glucose, creatinine (similar to plasma composition)
How is filtrate/ultrafiltrate different from plasma?
essentially no protein present – unless there is damage to filtration barrier
What is glomerular filtration rate (GFR)?
volume of plasma filtered (from glomerulus to bowman’s capsule) per unit time
What is the GFR range for healthy adults?
80-120 mL/min, or 115-173 L/day
What happens to GFR as you age? Why?
decreases
- reduced function of filtration
How does kidney disease affect GFR?
decreases GFR
What is filtration fraction (FF)?
fraction of plasma that is being filtered (overall quality of filtration function of kidney)
FF = GFR/RPF
What are the 3 layers of the glomerular filtration barrier?
- fenestrated endothelium – big openings found between endothelial cells
- glomerular basement membrane – determines what gets across barrier from blood, into tubule
- podocytes (visceral epithelium) – surround capillary
What specialized cells do glomerular capillary tufts require? Why?
intraglomerular mesangial cells
- glomerular capillary tufts are the only capillary beds not surrounded by interstitial tissue, therefore require unique structural support
How do intraglomerular mesangial cells function?
cells are connected to glomerular basement membrane, and have contractile properties that allow for regulation of GFR
contraction and relaxation change surface area available between podocytes for filtration to occur
What is the slit diaphragm?
thin structure near GBM that has proteins that connect adjacent podocyte foot processes
Is the slit diaphragm charged? Why?
negatively charged surface coat – helps with selectivity of barrier
What is podocin? What does it do?
protein component of slit diaphragm (filtration slits of podocytes) that helps with coordination and determination of what can can cross glomerular filtration barrier
What can cross the glomerular filtration barrier?
easier for smaller and positively charged substances (due to negative coating on barrier, which will repel negative charges) to cross
What substances are filtered out of blood plasma at the renal corpusce?
- Na+, K+, Cl- , Ca2+
- PO43- , H+ , HCO3- , NH4+
- H2O
- urea
- glucose
- creatinine, urobilinogen
- some proteins (trace amounts), amino acids
What is filtrate?
fluid and substances arriving to nephron from glomerulus – found in Bowman’s capsule
Can filtrate composition change?
NO – no way to change composition of fluid
Can filtrate be modified by reabsorption or secretion?
NO – only gets filtered
What is tubular fluid?
fluid in tubule along length of nephron, until it reaches end of collecting duct
Can tubular fluid composition change?
YES – lots of transport happening that will dramatically change fluid composition as we move along nephron
What substance is used to determine RPF?
RPF is physically measured – extrapolate what RBF would be from those values, using PAH
What substance is used to measure GFR?
inulin or creatinine
When looking at clearances, why do we use things that are largely excreted?
if largely excreted, we can remove renal vein component of equation (which is difficult to measure)
For GFR measurements, what’s important about the substance that is used?
important that it’s a substance that relies heavily on filtration for its excretion (ONLY FILTERED) – don’t want it to be something that is reabsorbed or secreted
Why is inulin or creatinine used to measure GFR?
~100% filtered (~100% excreted) – rely on filtration for their excretion
no tubular reabsorption or secretion
Is the amount of inulin or creatinine in an individual a good indication of filtration rate? Why?
numbers can fluctuate more depending on individual’s activity level – less precise measurement, but still good indication of filtration rate
How is the amount of inulin in an individual determined?
known amount is injected into person, then we can measure it in blood once it’s equilibrated, and in urine once it’s excreted
What is creatinine?
breakdown of skeletal muscle
assessed routinely if investigating kidney function
What are the 3 clearance measurements used to determine filtration fraction?
C_PAH
C_In
C_Cr
What is the filtration fraction of a healthy individual?
FF = GFR/RPF = 0.20
~20% of plasma delivered to kidney is filtered into the nephrons
What would happen to the filtration fraction if an individual was in some type of disease state (scarring/damage to filtration barrier)?
not as able to pass substances across the barrier, GFR would be impaired (lower)
amount of blood being delivered (RBF) needs to know the ratio between GFR and RPF
RPF is unchanged because we are still able to secrete PAH
FF would be LOWER
What does GFR tell us?
how much of the plasma delivered to kidney actually gets filtered
Is creatinine normally found in the body?
creatinine found (and cleared normally) in everyone’s body, or can inject to get more controlled assessment of filtration rate
What is GFR?
volume of fluid that filters into Bowman’s capsule per unit time
~180 L/day crosses barrier
What is GFR influenced by?
pressure
What are the 3 types of pressure that influence GFR?
- hydraulic pressure (PH or PGC)
- colloid osmotic pressure / oncotic pressure (πGC)
- fluid pressure within Bowman’s capsule (PBS)
What is hydraulic pressure?
blood pressure that favours movement of substances from capillary into Bowman’s capsule
What is colloid osmotic pressure / oncotic pressure?
pressure that opposes movement of substances from capillary into Bowman’s space
- comes from proteins found in blood vessel
- no oncotic pressure for Bowman’s space because there should not be protein in there
What is fluid pressure within Bowman’s capsule?
favours movement of substances from tubule back into capillary
Why is GFR always positive?
hydraulic pressure is going to be so great, that filtration is essentially always occurring
positive = favours fluid moving out of glomerular capillary to Bowman’s space (ultrafiltration occurs)
as indicated by Starling equation for GFR
Resistance Changes in Renal Arterioles Alter RBF and GFR
How can the amount of filtration that occurs across the membrane be modified?
- modify blood that will get delivered to kidneys
- modify amount of filtration that will occur at kidneys
(can modify these separately from one another)
Resistance Changes in Renal Arterioles Alter RBF and GFR
What happens to P_H, GFR, and RBF if there is increased resistance (vasoconstriction) of efferent arteriole?
increases PH and GFR
- point of resistance added after glomerulus
- pressure in glomerulus increases – makes it harder for blood to get past that point
- leads to increase in GFR
decreases RBF
- increased resistance of blood going through kidney → too much traffic in kidney → blood goes to other sections of the body
Resistance Changes in Renal Arterioles Alter RBF and GFR
What happens to P_H, GFR, and RBF if there is increased resistance (vasoconstriction) of afferent arteriole?
decreases RBF, PH, and GFR
- point of resistance added before glomerulus
- more difficult to get blood into kidney – resistance of overall pathway going into kidney is still high
- because of increase in resistance, pressure in glomerulus decreases to help reduce filtration
What happens to P_GC, GFR, and RBF when afferent arteriole constricts?
PGC decreases
GFR decreases
RBF decreases
What happens to P_GC, GFR, and RBF when efferent arteriole constricts?
PGC increases
GFR increases
RBF decreases – because radius is reduced, blood going to kidney increases overall, therefore RBF will still go down
What happens to P_GC, GFR, and RBF when efferent arteriole dilates?
PGC decreases
GFR decreases
RBF increases – because it’s easier for blood going into glomerular capillary to take that path (increased diameter), therefore PGC decreases
What happens to P_GC, GFR, and RBF when afferent arteriole dilates?
PGC increases
GFR increases
RBF increases
(similar to efferent arteriole dilation) because resistance of system is decreased and it is easier for blood to get through, there is increase in RBF
- but because it will be easier for blood to get into capillary (but hasn’t changed how easy it is to get out), PGC increases → GFR increases
Why is regulation of GFR over a wide range of mean arterial blood pressure important?
important for protection of structural integrity of glomerulus
over wide range of mean arterial pressure, there is relatively stable RBF and GFR
- important because glomerulus is very susceptible to damage with large pressure increase (due to less structural integrity – recall: no interstitial tissues)
What are the two types of regulation of GFR?
intrinsic (autoregulation)
extrinsic
What are the two types of intrinsic regulation of GFR?
- myogenic response
- tubuloglomerular feedback
What happens in the myogenic response?
(increase in blood pressure → diameter of afferent arteriole increases/stretches)
- reflexive vasoconstriction to decrease it back to original diameter – occurs very rapidly to protect glomerular capillary tissue
What is tubuloglomerular feedback mediated by?
interaction between distal component of nephron and glomerulus
What are intrinsic mechanisms of GFR regulation largely responsible for?
maintenance of stable GFR (even with changes in mean arterial pressure) over MAP range of 60-130 mmHg in humans
What are the two types of extrinsic regulation of GFR? What do they do?
hormones – act primarily on afferent arteriole to regulate tone, and help protect glomerulus
neural – sympathetic neurons innervate afferent arteriole to help with regulation of vascular tone
Which arteriole is preferentially regulated? Why?
preferentially regulate afferent arteriole over efferent arteriole because it is before the glomerulus
- main goal of GFR regulation is to protect structural integrity of GFR by preventing rapid increases in pressure within capillary tuft
- regulation afterwards can be helpful, but not as protective
What is the myogenic response?
most rapid response to alterations in RBF, with almost immediate onset and completion within 10 seconds
- accounts for ~50% of autoregulation response
- occurs in afferent arteriole
Myogenic Response
SEE PRINTED DIAGRAMS
Where are mechanosensitive ion channels found?
cell membranes of vascular tissue
How does TMP change during the myogenic response?
- increase in mean arterial pressure leads to increase in TMP in arteriole, which is what we would see in response to blood pressure increase
- decrease in TMP is equivalent to reduction in mean arterial pressure that results in reduced TMP of that arteriole
What happens to Ca2+ during the myogenic response?
- intracellular Ca2+ changes in response to TMP change
- when pressure increases, Ca2+ available within cytosol increases
- Ca2+ stays high until TMP decreases, which also decreases Ca2+
What happens to vessel diameter during the myogenic response?
- diameter increases when TMP increases
- diameter decreases with sustained Ca2+ release
- diameter decreases when TMP decreases
What is tubuloglomerular feedback?
- begins acting 6-30 seconds after alteration in RBF, with full response within 30-60 s
- accounts for approximately 35-50% of autoregulation response
- helps make sure we don’t have sustained increased pressure within glomerular capillary
- detected in more distal portion of nephron and communicated back to afferent arteriole
Where is the tubuloglomerular feedback signal generated?
interaction between macula densa (just before we get to distal tubule) with efferent and afferent
Tubuloglomerular Feedback (TGF)
Why does an increase in (faster) tubular flow result in more [Na+] and [Cl-] in tubule fluid in loop of Henle?
more [Na+] and [Cl-] can travel through this section and continue to macula densa b/c it’s more difficult for reabsorption to occur due to increase in flow rate
What are the two hormones involved in extrinsic regulation of GFR?
angiotensin II
epinephrine
there are also others
What does angiotensin II do?
helps with vasoconstriction
What does epinephrine do?
- helps with vasoconstriction of afferent arteriole → minimizes increase in pressure in glomerulus
- cause intraglomerular mesangial cells to contract – contraction moves podocytes closer together and reduces surface area for filtration to occur
Why do both hormones and sympathetic neurons reduce RBF and GFR?
they vasoconstrict afferent arteriole
How do sympathetic neurons extrinsically regulate GFR?
- synapse onto afferent arteriole vascular smooth muscle
- binds to α1-adrenergic receptors
- release norepinephrine → vasoconstriction of afferent and efferent arterioles (but for regulation of GFR, afferent arteriole is main target)
- results in decreased RBF and GFR
What is the myogenic response?
most rapid response to alterations in RBF, with almost immediate onset and completion within 10 seconds
- accounts for ~50% of autoregulation response
- occurs in afferent arteriole
Myogenic Response – Mechanism
see notes
What is tubuloglomerular feedback?
begins acting 6-30 seconds after alteration in RBF, with full response within 30-60 s
- accounts for approximately 35-50% of autoregulation response
- helps make sure we don’t have sustained increased pressure within glomerular capillary
- detected in more distal portion of nephron and communicated back to afferent arteriole
Tubuloglomerular Feedback – Mechanism
see notes
