filtration and clearance grassl Flashcards
glomerular filtration
-the process of plasma being filtered across the glomerulur capillary to form a protein free ultrafiltrate in Bowmans space
-the starling forces/ diff in oncotic and hydrostatic forces across the glomerular capillaries drive the net efflux of the plasma ultrafiltrate
-organic and inorganic anions and caions are freely filtered across the glomerular capillaries and exist in same conc in plasma and ultrafiltrate. only diff is that the plasma has proteins and ultrafiltrte doesnt
-GFR: 125ml/min aka 180L/day
ECF volume is 14 L, so more than 10X the ECF volume is filtered everyday. equivelent to filtering the total ECF every 2 hours.
Starling forces drive glomerular filtration
Filtration rate= Kf[(Pgc-Pbs)-(πgc-πbs)]
Kf= filtration coefficient
P= hydrostatic pressure π= oncotic pressure
gc- glomerular capillary bs=bowmans space
- the filtration coefficient is based on capillary hydraulic conductivity and surface area for filtration
- oncotic pressure in an osmotic pressure due to presence of proteins
- Pgc=45-50 at beginning of glomerular capillary and only decreases around 3mmHg to 41-47mmHg, even though alot of plasma volume is lost. Occurs by constriction of the EFFERENT arteriole.
- post capillary efferent constriction is unique to the glomerular and not systemic capillaries.
- πgc=25mmHgat beginning of capilary and increases to 35 at end.
- Pbs=10mmHg.
- πbc=0. goes up alot though in nephrotic syndrome
- starling forces along the glomerular capillary: Pgc stays about constant (bc of constiction of the efferent arteriole). Pbs stays about constant around 10. π bc stays constant at 0, but πgc increases! this is bc of the plasma that leaves.
- the Puf increases along the glomerular capillary network. the driving force favors filtration for awhile. eventually the forces balance and there is no net filtration.
the glomerular barriers to filtration
- endothelial cells of the glomerular capillaries act like a sieve ad restict passage of cellular elements into Bowman’s space
- the capillary basement membrane that endothelial cells sit on act as a resticition to filtration to large solutes. it is highly negatively charges, so proteins cant get thorugh bc they are so large and bc they have such a high negative charge. canions easily get thorugh and small anions can go through also.
- podocytes of the visceral epithelial layer of bowmans capsule have foot processes that cover the glomerular capillaries. contiguous foot processes are seperated by filtration slits, and anionic chargrs further restrict filtration of anionic proteins but not smaller organic or inorganic ones.
size dependance of solute permselectivity at the glomerular barrier
[S]bc/[S]plasma
- H20, glucose, NaCl, and Inulin (small pentomere of sugar molecule used to measure glomerular filtration) all have a filerability of around 1 bc they are so small. myoglobin is a little bit larger, hemoglobin is larger stil, and albumin is largest. albumin has filterability around 0 bc its so large.
- in conc of solute in bowmans space equals conc of solute in plasma, then the filterability is 1. if a solute is less filerable bc its large, the ratio will be less than 1.
- if we increase size of a molecule, you see a decrease in its concentration in bowmans space.
dependance of filterability on charge and size
- filterability=clearance ratio. depends on charge and size
- inulin is freely filtered. -negative charge from the foot processes and from the basement membrane impedes flow of negatively charged solutes
- large lomecules arent filtered as well as small. at a given radius though, a cation will be filtered and cleared much metter than a neutral solute or an anion solute
- if you remove the negative charge from the glomerular barrier, you ncrease the passage of anions. this occurs with increased filtration of plasma proteins in NEPHROTIC SERUM NEPHRITIS
renal hemodynamics
- cardiac output CO is HRXSV and is tht total blood volume. CO at rest is equivelent to the blood volume, (7% of the BW) and around 20% of the CO perfuses the kidney
- so CO is 5-6 L a min, 1-1.2 L is RBF (renal blood flow).
- RPF (renal plasma flow) is 55% of RBF, so 600-720 mL and 20% of the RPF is filtered by the glomeruli, so 125mL is filtered by glomeruli per minute. equals to 180L a day
- FF=filtration fraction. is a measure of the factor is plasma going through the kidney filtered at the glomerulus. equals to (GFR)/(RPF) = 125mL/min/600ml.min=== 20%
-GFR stays constant at 180L/day. rate and volume of urine excretion varies according to rate and volume of fluid consumed. this changes the volume and solute conc in ECF and kidneys work to maintain the ECF within normal limits by acting on volume and solute composition of the glomerular filtrate.
GFR increases w/ increasing RPF and FF (filtration fraction) decreases w/ increasing RPF
FF= GFR/RPF so if RPF goes up, FF has to go down
-as lasma flow increases, GFR increases. FF decreases,
-in acute and chronic renal failure, filtration stops, so you dont make urine
-curvilinear relationship bw GFR and RPF shows that a greater fraction of RPF is filtered at lower rates of RPF and a smaller fraction filtered at a higer rate
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effect of changing starling forces on RPF and GFR
-confusing.
-fluid reabsorption in the post glomerular peritubular capillaries
- starling force drive fluid reabsorption from the interstitial space into the peripubular capillaries. the oncotic pressure difference (πpc-πis) drivinf fluid absorption exceeds the peritubular capillary hydrostatic pressure difference opposing it.
- Ppc=20 (constriction of the preceding efferent arteriole_
- πpc-35mmHg (the filtration of plasma is concentrating the plasma proteins)
- Pis=6-10mmHg
- πis=4-8 mmHg
- net pressure difference driving net fluid reabsortion/filtrations is
(Pps-πpc)-(Pis-πis) - (20-35)-(8-6)–17mmHg
- negative sign inicates pressure driving fluid into the peritubular capillary and posiitve would be pressure driving fluid out.
- i million nephrons and each have their own peritubular capillary network
- tubular fluid in lumen→ tubular cells→interstitial fluid→peritubular capillary
- reabsortion is drection of solute and fluid movememtn from the lumen of the tubule back into the capillary! must go across barries, can go either across or between cells
net absorptive pressure along peritubular capillaries
-forces favoring reabsortion are: Pis+πpc
-forces against: Ppc+πis
the net absortive pressure along the peritubular capillary goes down as you move along distance
Glomerular filtration rate
-measing GFR can give you an index of number of functioning nephrons in kidney disease
-renal failure starts when GFR decreases below 20mL/min or you lose functional use of 85% of nephrons
-renal clearance: virtual volume of plasma from which a solute is complete removed from the plasma by the kidney per unit time. Renal clearance is in ml/min. Renal clearance can be used to measure GFR if the renal handing of the solute is: freely filteted at the glomerulus, not reabsorbed in any segment of the nephron, not secreted at any segment, not synthesized or metabolized by kidney.
excretion(clearance)=filtration(GFR)-reabsortion(0)+secretion(0)
-amt of sulte filtered=GFR=plasma conc X rate of plasma filtration==
amt of sulte filtered= Ps X GFR
-amt of solute excreted=urine conc of solute X rate of urine flow
amt of solute excreted= Us X V
-amt of solute filtered/time= amt of solute excreted/time:::
Ps X GFR = Us X V
-GFR= (Us X V)/(Ps)
-GFR= urine conc of solute X rate of filtration / plasma concentration of solute
-filtered load f solute is the amt of solute filtered over time
solutes used to measure GFR
exogenous: : -inulin- fructose polymer given by IV infusion to maintain constant plasma inulin and meaused accurately in urine
- endogenous: creatinine from skeletal muscle metabolism- in absense of strenuous exercise or disease, a constant amt of creatinine diffuses from skeletal muscel to plasma
- creatinine production is constant, so an increase in plasma creatinine equals a decreased clearance, which means a decreased GFR resulting from decreased number or functioning nephrons/ acute renal failure
- as kidneys recover from renal failure, a decrease in plasma creatine is an increase in clearance and increase in GFR
- so, measuing plasma creatinine normal being 1mg/100ml, indicates an increase or decrease in GFR bc of kidney disease
solute clearance
Cs= (Us X V)/Ps
Cs= clearance of solute Us= urinary solute conc V= volume of urine collected in T minutes Ps= conc solute on plasma
if 99-99.5% of filtered sodium is reabsorbed, then the clearance of sodium would be 1 ml/min or less
clearance ratio
- if a solute clearance is less than the clearance of inulin/ creatinine, indicates the solute is not freely filtered at the glomerulus, or if it is freely filtered then net solute reabsortion has occured
- asolute clearance greater than inulin/creatinine indicates net secretion of solute has occured
- Cs/Cin less than 1 is solute reabsorption
- Cs/Cin greater than 1 is solute secretion
fractional excretion of water
-fractional excretion of water is urine flow/ GFR
-fraction of glomerular filtrate not reabsorbed from the tubular fluid. appears as urine
-if inulin is 100X more concentrated in urine than plasma, than only 1% filtered water is eliminated in urine.
Pin/Uin= 1/100= 1%
-FEH2O easily measured from urine and plasma sample and creatinine levels
-in water and Na balance, 99% of filtered Na and water is reabsorbed
