Lect 6: Filtration & Clearance Flashcards
What is glomerular filtration?
process of filtering plasma across the glomerular capillaries to form a protein-free ultrafiltrate. The filtrate is not urine:
all solutes in plasma exist in the glomerular filtrate at the same conc as they are in the plasma
NOT REABSORPTION, only filtration
GFR is normal
125 mL/min or 180L/day
Starling Forces drive Glomerular Filtration
Filtration rate is Kf (Pgc-Pbs)–(Pogc-Pobs)
Pobs is usually 0
Pgc–Pbs is
difference in hydrostatic pressure inside the glomerular capillary and Bowman’s space
Oncotic
difference in oncotic pressure inside the glomerular capillary and bowman’s space
What is the Pgc?
it is around 45-50mmHg at the beginning of the glomerular capillary and decreases to 41-47mmHg at the end of glomerular capillary.
The glomerulus has the capacity to increase or decrease the surface area available for filtration.
as you decrease the flow of blood thru the glomerular capillary, the surface available for filtration decreases and GFR decreases
not an arteriole-venous; it is ARTERIAL Blood
Glomerular Barrier to Filtration
- Endothelial cells
- Capillary Basement Membrane
- Podocytes
Endothelial cells of glomerular capillarier
sieve the passage of cellular elements into Bowman’s space;
Basement Membrane on which the endothelial cells sit
negatively charged and repels anionic charges that are very large (such as albumin); PREVENTS filtration of plasma mambrane
Podocytes
cover the outer surface of glomerulus; where two of them meet there is slit diaphragm where anionic charge further restricts filtration of anionic proteins, but not smaller organic and inorganic anions
Where does the ultrafiltrate collect?
in Bowman’s capsule. Then it exits via the efferent arteriole
Size dependence of solute permselectiveity at the glomerulus
size vs. filterability
filterability is measured as the ratio of solute conc in BS/solute conc in plasma
substaces such as water, NaCl, Inulin are freely filtered and very small in size when compared to Hemoglobin or myoglobin or Albumin
If something is freely filtered it
exists at the same conc in BS as it does in plasma solute conc BS/solute conc in plasma=1
==>such as water and inulin
The larger the molecule
the less it will be filtered; so none of the molecule is in BS. They are all tied up in plasma
Charge
the negative charge on the foot processes and basement membrane impedes the passage of negative charged solutes.
–so lots of cations of a given size would be able to pass
–Removing the negative charge from the glomerular barrier increases the passage of anions such as occurs with increased filtration of plasma proteins in nephrotic serum nephritis
Filterability equals
clearance ratio (Cx/Cinulin); inulin is freely filtered
Why is regulation of cardiac output important?
P= Q x R
Total Peripheral Resistance (TPR) and CO determine BP. If TPR decreases, CO increases to maintain BP and vice versa. BP gradient highest in aortaBP lowest right as it enters heart.
BP= CO x TPR
CO=Total Blood Volume (5L)
20% of this goes to the kidney to become ultrafiltrate… bc it manages the volume and osmolarity of ECF. ECF broken down into plasma flow. 20% of this RPF is GFR. This is the filtration fraction
FF= GFR/RPF
125mL/min/600mL/min = 0.2
When your urine output is 1mL/min
you are dehydrated; urine trying to retain water as uch as possible. When you are overhydrated you pee out a lot. Urine output changes based on your fluid balance
(FF-GFR/RPF) GFR increases with increasing RPF
and FF decreases with increasing RPF (bc it has less time with the stuff to filter???)
As RPF increases GFR increases until it reaches a plateau (bc all the surface area is maximally filtering).
So slope (GFR/RPF, which is equal to FF) is greater than 1. FF is the fraction of plasma flow filtered at the glomeruli. Accordingly, the FF is higher at low RPF (bc you don't want it to saturate?) and lower at high RPF. This maintains the GFR at levels necessary for renal function when RPF is compromised due to dz.
Effect of Changing Starling forces on RPF and GFR: Effect of AFFERENT arteriolar constriction on these two
it decreases both GFR & RPF -
this will decrease the hydrostatic pressure (necessary for squeezing the filtrate out) and depending on the magnitude of the decrease, it may even decrease the capillary surface area. When the RPF rate is less than normal the filtration surface area is reduced!
Effect of Changing Starling forces on RPF and GFR: Effect of EFFERENT arteriolar constriction on these two
Effect on RPF: decreases
Effect on GRF: increased bc you increased gcHydrostatic pressure (upstream) - so you will squeeze more filtrate out of the glomerulus into Bowman’s space. So this will happen at a faster rate
Effect of Changing Starling forces on RPF and GFR: When both afferent and efferent arterioles are constricted
So long as flow is sufficient to allow filtration across the entire capillary bed, RPF will decrease but there will be NO CHANGE in GFR because the hydrosatic pressure didn’t change. As long as the starling force is sufficient to drive filtration you will not get any change in GFR.
Effect of Changing Starling forces on RPF and GFR:
increasing plasma oncotic pressure
Always think in terms of Starling forces. What is the relationship of oncotic pressure to hydrostatic pressure if you increase oncotic pressure?
This increased oncotic pressure resists filtration. If it is increased it will resist hydrostatic pressure causing it to decrease. This decreases GFR but has NO EFFECT on renal plasma flow
If you decrease plasma protein (oncotic pressure)
you will be reducing RPF which increases GFR (No effect on RPF)
If you obstruct the ureter this increases the Hydrostatic pressure in Bowman’s capsule
sending stuff up back into the glomerulus. This decreases the filtration rate (GFR) but it will not affect RPF but it will decrease
Fluid Reabsorption in the Post-glomerular capillaries
the fluid exiting the glomerulus that has been filtered will not have higher osmolarity because you’ve not lost volume. It will have a higher oncotic pressure though
Pathway for solute and fluid reabsorption
tubular fluid in lumen–>tubular cell–>interstitial fluid–>peritubular capillary
Each nephron has its own peritubular capillary network exiting the glomerulus of the same nephron. The peritubular capillary network lies adjacent to the basolateral or blood side of the tubular epithelial cells, Water and solutes transported across the tubular epithelial cells from the lumenal side to the basolateral side are returned to circulation by absorption or uptake into the peritubular capillaries
Over here the oncotic pressure dominates the hydrostatic pressure.
So the numbers are negative, indicating reabsorption
hydrostatic pressure outside and oncotic pressure inside capillary favoring reabsorption IS GREATER than the hydrostatic pressure inside and oncoti pressure outside. This drives reabsorption inside the the capillary
Renal Clearance of a substance is
the volume of plasma from which a solute is completely removed from the plasma by the kidney per unit of time. Renal clearance is a rate (mL/min)
Under what conditions can renal clearance be used to measure GFR:
- freely filtered at the glomerulus
- not reabsorbed in any segment of the nephron
- not secreted in any segment of the nephron
- not synthesized by the kidney
- not metabolized by the kidney or changed chemically
all of this means that the amount filtered
For a solute, the amount filtered/time will be equivalent to
the amount excreted/time in the urine
amount of solute filtered is
plasma conc of solute times rate of plasma filtration into BS
(Ps x GFR)
amount of solute excreted
urine conc of solute x rate of urine flow
Us x V
Set Us x V/Ps x GFR to get GFR equals
Us x V/Ps.
This is the renal clearance (125ml/min)
Inulin satisfies the requirements
it can be infused.
Creatinine can also be used. It is endogenous and is constantly leveled. If the clearance of creatinine goes down it indicates that the kidneys are not working properly because they are not filtering.
if the clearance of creating goes up then you know that the kidneys are working again (and creatinine levels are going down)
Clearance ratios: if the Cs/Cin is less than 1. what does this indicate?
NET solute reabsorption
Clearance ratios: if the Cs/Cin is greater than 1. what does this indicate?
NET solute excretion into the tubular fluid
Solute Clearance Ratio
Cs= U x V/ Ps
Fractional Excretion of Water
is the fraction of filtrate that is NOT absorbed from the tubular fluid along the nephron so it appears as urine
What is the FeH20?
it is the ratio of urine flow rate to GFR
Fh20= V/GFR
where GFR= Cin = Uin x V/Pin
Fh20 = V/Cin = V x Pin/Uin x V = Pin/Uin
Inulin is neither reabsorbed from nor serceted into the tubular fluid and its conc in the urine rises directly form the amount of water reabsorption occurring in the nephron
If inulin is 100 fold more conc in the urine than plasma
Pin/Uin = 1/100 = 0.01; so only 1 percent of the filtered water is eliminated as urine
Fractional Excretion of a solute
is the fraction of filtered solute which appears in the urine. It may be estimated as the ratio of solute clearance to GFR. You use the Creatinine clearance to estimate GFR
FEs = Cs/Ccreat = Us x V/Ps / Ucreat x V/Pcreat
= Us x P creat/ Ucreat x Ps
What is another way to quantify Fes?
1–FE so approx 99% of Na and H2O are reabsorbed
Autoregulation of Blood Flow
even though mean arterial pressure changes, Renal blood flow does not.
Renal vascular resistance resistance increases and decreases (autoregulation) with increased and decreased mean arterial pressure, keeping RBF relatively constant
what is the equation?
RBF = renal arterial pressure–renal venous pressure/ renal vascular Resistance
myogenic response
tubuloglomerular feedback at the macula densa cells sensing an increase or decrease in GFR and causing increased or decreased resistance (constriction) of afferent arteriole, returning GFR to normal values
autoregulation is intrinsic to kidneys.
when BP rises, what happens to vascular resistance in order to keep flow constant:
an increase in resistance to flow or a decrease in BV diameter
