Filtration and Clearance Flashcards
glomerular filtration
- the process by which plasma is filtered across the glomerular caps to form a protein free ultrafiltrate in bowmans space
- differences in oncotic and hydrostatic pressure across the glomerular capillaries drive the net efflux of a plasma ultrafiltrate
- GFR is approx 125 ml/min or 180 L/day
- more than 10 fold of the extracellular volume and equivalent to filtering entire ECF evert 2 hours
- serves the purpose of maintaining ECF volume and solute composition within narrow limits by rapidly responding to correct changes in ECF volume and solute comp
Kf
-filtration coefficient of the glomerular capillary and is the product of the cap hydraulic conductivity and the SA available for filtration
filtration rate
- driven by starling forces
- = Kf [(Pgc-Pbs)-(pigc-pibs)]
- when DF favoring and opposing glomerular filtration become equivalent toward the efferent end of the glomerular cap, filtration stops
- hydrostatic pressure of GC starts bigger and then oncotic pressure of GC smaller (out then in)
- Pgc and pi BS favor filtration first
- then Pbs and pi GC favor stopping
Pcg-Pbs
-difference in hydrostatic pressure inside the glomerular cap and bowmans space
pi gs- pi bs
- difference in oncotic pressure inside the glomerular cap and bowmans space
- presence of proteins
Pgc
- 45-50 mm Hg at beginning of cap and decreases 3 to 41-47 at the end
- occurs despite a decrease of plasma volume and is due to post cap efferent ateriole constriction
Pi gc
- 25 mm Hg at the beginning of cap and increases to 35 mmHg at the end
- due to plasma filtration and concentration of plasma protein
Pbs
-10 mm
pi bs
- 0
- increases in nephrotic syndrom due to filtration of plasma protein
glomerular barrier to filtration
- endothelial cells of glomerular caps restrict passage of cellular elements into bowmans space
- cap basement membrane restricts filtration of solutes larger than 1 kDa
- an anionic charge favors filtration of cations and restricts filtration of anionic proteins
- podocytes of the visceral epithelial layer of bowmans cap have foot processes covering the glomerula caps
- contiguous foot processes are separated by filtration slits where anionic charge further restricts filtration of anionic proteins, but not smaller organic and inorganic anions
- glycoproteins with neg charge also cover podocytes, filtration slits and slit diaphragms favor filtration of small cationic solutes
glomerulus and Bowman’s capsule
- permselectivity of the glomerular barrier is determined by the size and charge of the solute
- water and solutes with a diameter of less than 4 nm (effective molecular radius of less than 2 nm) are freely filtered
size dependence of solute perselectivity at glomerular barrier
- water, salt glucose, inulin are freely filtered, same concentration in plasma and filtrate
- as radius increases, filtration decreases
dependence of filterability on charge
- neg charge on BM and foot impedes passage of neg solutes (proteins)
- allows positive
- removing negative charge from barrier allows neg ions to pass
- happens with increased filtration of plasma proteins in nephrotic serum nephritis
renal hemodynamics
- CO is 5-6 L/min, 7200-8640 L/24 hrs
- renal blood flow (RBF)- 1-1.2, 1440-1728
- RPF-600-720 ml, 860-1040 L/24 hrs
- GFR 125 ml/ min, 180 L/24 hrs (constant)
- urine output 1ml/min to 10 ml/min
- 20% of CO perfuses kidney, CO is 7% of body weight
RPF
- 55% of RBF
- 20% of RPF is filtered at glomeruli
- fraction of RPF filtered at glomeruli is filtration fraction
FF
GFR/RPF
-0.2
amt filtered
- 180 L of plasma per day, more than 10x ECF vol
- constant vol and solute comp
GFR
- increases with increasing RPF
- FF decreases with increasing RPF
- if increase RPF, GFR increases and FF decreases
- max GFR at 600 ml/min
- as plasma increases, more SA is filtering
- normal 125 ml/min at plasma flow of 600 ml/min means 20% FF
afferent arteriolar constriction
- decrease Pgc
- RPF decreases and GFR decreases
efferent arteriolar constriction
- increase Pgc
- RPF decreases
- GFR increases
afferent and efferent arteriolar constriction
- RPF decreases a lot
- RPF dependence of GFR is a function of SA, which is more or less maximal at normal or above normal rate of RPF
increase plasma protein
- increase pi gc
- GFR decreases
decreased plasma proteins
-GFR increases
obstruct ureter
- increases Pbs
- GFR decreases
fluid reabsorption
- post glomerular and peritubular caps
- from interstitial space into peritubular caps
- peritubular cap oncotic pressure difference driving fluid absorption exceeds peritubular cap hydrostatic pressure difference.
Ppc=20 (constriction of preceding efferent arteriole), pi pc= 35 (filtration of plasma concentrates plasma proteins)
Pis= 6-10, pi is = 4-8
(Ppc-pipc)-(Pis-piis) drives reabsorption or filtration
- neg 17 means net reabsorption into peritubular cap (lies on basolateral side (blood))
path through kidney
-tubular fluid in lumen to tubular cell to interstitial fluid to pertibular capillary
Glomerular Filtration Rate
- measurement can provide index of the number of functioning nephrons in kidney disease
- renal failure begins when GFR decreases to below 20 ml/min or a loss of function of 85% of nephrons
renal clearance
- virtual volume of plasma from which a solute is completely removed from the plasma by the kidney per unit of time
- ml/min
renal clearance can be used to measure GFR when
the renal handling of the solute is:
- 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
math
-for solute with correct properties, the amount of solute filtered/time with be equivalent to the amount of solute excreted/time in the urine
-filtration=excretion
-amt filtered=plasma concentration of solute x rate of plasma filtration
= Ps(plasma concentration) x GFR
= urine concentration x rate of urine flow
= Us (urine concentration) x V
GFR=UsxV/Ps
solutes used to measure GFR
- inulin is exogenous- given by IV infusion to maintain constant plasma and measured accurately in plasma and urine
- creatinine is endogenous-in the absence of strenuous exercise or disease a constant amy of creatinine/time diffuses from skeletal muscle to plasma
- when production from muscle is constant, increased plasma concentration means decreased clearance from the plasma, means decreased GFT and acute renal failure
- if plasma creatinine is increased, clearance is decreased
- normal is 1 mg/ 100 ml
clearance
C= Us x V/ Ps
- if a solute is freely filtered and 50% of the filtered solute was reabsorbed, then amt excreted would be 50% of the amt of solute filtered as indicated by decreased Us
- kidneys only clearing 62.5 ml of plasma/min of solute
- if 99-99.5% of sodium is reabsorbed, the clearance would be 1ml/min or less
clearance ratios
- clearance of anything may be more or less than creatinine/inulin
- renal handling of a solute may be only reabsorbing, only secretion, or both, in same or different segments of nephron
- when both occur, difference in solute reabsorption and secretion determines net reabsorption or secretion
- solute clearance less than creatinine indicates the solute is not freely filtered or if it is, net reabsorption has occurred
- clearance greater than creatinine indicates that net secretion has occurred
- less than 1 equals reabsorption
fractional excretion of water
- fraction of the glomerular filtrate not reabsorbed from the tubular fluid along the nephron and therefore appearing in urine
- ratio of urine flow rate to GFR
=V/GFR where GFR=C=U xV / P
=V/C(in)= (VxP)/ (UxV)= Pin/Uin
- plasma to urin inulin concentration ratio
- inulins concentration in urine arises directly from the amt of water reabsorption occurring in the nephron
- if inulin is 100x more concentrated in urine–> Pin/Uin= 1/100= 0.01- 1% of filtered water being eliminated (99% reabsorbed)
- can also use creatinine
fractional excretion of solute
- for any solute filtered, it is the fraction of filtered solute that appears in uring
- estimated as ratio of clearance to GFR
- creatinine clearance used to estimate GFR, fraction of filtered solute is easily determined by measurement of solute and creatinine concentration in plasma and urine
=(Usx Pcreat)/(Ucreat xPs)
water and salt
- when in balance, 1 % of filtered water and Na appears in the uring
- in neg water balance- fraction of water is less than 1, Na still one
- over hydrated- water to 5, Na still 1
fractional reabsorption
- fraction of water or solute that is reabsorbed and doesn’t appear in urine
- 1- FE
- in water and Na balance, 99% of filtered Na and water are reabsorbed
autoregulation of blood flow
- renal blood flow maintained at constant
- 1.2 L/min
- across wide range of MAPs
- maintains GFR constant
- renal vascular resistance increases and decreases with increased and decreased MAP
- RBF=BP/R
- autoreg due to:
- myogenic response of renal vasculature to pressure changes
- tubuloglomerular feedback at the macula densa cells sensing an increase or decrease in GFR and causing increased or decreased resistance of the afferent arteriole, returning GFR to normal
- intrinsic to kidney and occurs in absence of autonomic innervation to kidney
