Glomerular Filtrattion I Flashcards
Filtration
Removal of dissolved substances and water from plasma
. Glomerulus is filter
Reabsorption
. Recapturing filtered solute and H2O
. Returned to plasma
. Process occurs in tubules
Secretion
. Movement of solute from peritubular capillaries into tubules
. Some substance both filtered and secreted
Excretion
.removal of solute and H2O from body in urine
. Solute gets into urine by filtration and/or secretion
Concentration and dilution
. Determines whether urine will by hypo-, iso-, or hyperosmotic
Glomerular filtration rate
. GFR = Kf [(Pgc-Pbs) - (pigc - pibs)]
. Rate at which fluid is removed from plasma by nephron is single nephron GFR
. Normal GFR is just the sum of all single-nephron rates in both kidneys
. Expressed in ml/min or L/24 hr
. Pgs = glomerular capillary hydrostatic pressure
. Pbs = Bowman’s space hydrostatic pressure
.pigc = glomerular capillary oncotic pressure
. Pibs = Bowman’s space oncotic pressure
Unique characteristics of glomerular capillaries
. Filtrate is nearly protein-free the oncotic pressure in Bowman’s space is 0
. Oncotic pressure in capillaries rises as plasma moves through it since protein is retained
. Capillary hydrostatic pressure shows slight decline along capillary
. Kf is 100x greater than systemic capillaries and hydrostatic pressure is 2x greater
. Filtration occurs over length of capillary loop (no reabsorption) of fluid occurs in capillaries
. High rate of filtration due to high Kf
Excretion equation
. Excretion = urine conc. Of X x urine flow rate (ml/min)
. When normalized for plasma conc. It yields the clearance of the substance from the blood
Renal clearance of substances from blood
. Clearance gives net rate of loss from blood
. Cx = (Ux x V)/Px
. V = urine flow rate in ml/min
. Ux = urine conc. In mg/ml
. Px= plasma conc. In mg/ml
.clearance is ml of blood plasma completely cleared of a given substance in 1 minute
. Typically less than renal plasma flow
. Clearance used to measure GFR and renal plasma flow (RPF)
. Can be used to determine whether there is net reabsorption or secretion of a freely filtered substance
How clearance can be used to measure GFR
. Clearance of a substance that is only filtered is equal to GFR
. Used if substance is not metabolized by the kidney, is freely filterable, and is neither secreted nor absorbed
. Amount of something excreted must equal the amount of it filtered
. Filtered load: GFR x plasma conc. of substance
. Excretion: urine conc. Of substance x urine flow rate (V)
Substances used to measure GFR via urinary clearance
. Inulin: classic standard
. Nonradioactive iothalamate; widely used, can be used to measure GFR via plasma clearance alone
. Creatinine: released from skeletal cells at constant rate, clearance is estimate of GFR
How to measure GFR via plasma clearance
. Bolus IV infusion of marker substance, many plasma samples over time
. Clearance from amt of marker infused divided by area under curve of plasma conc. Over time
. Disadvantage is amt of time to generate plasma clearance curve
Substances used to measure GFR via plasma clearance
. Iohexol: radiographic contrast agent used to measure GFR using plasma clearance
. Can also be used for urinary clearance
. Iothalamate: used more often for urinary clearance than plasma clearance
Normal ranges of creatinine clearances as estimate of GFR
. Men: 140-200 L/day, 70 +/- 14 ml/min/m2, 97-140 ml/min
. Women: 120-180 L/day. 60 +/- 10 ml/min/m2, 83-125 ml/min
.
Creatinine clearance qualities
. Produced at relatively constant rate by skeletal muscle and the rate is proportional to muscle mass
. Estimate and not true measure bc small amount of creatinine is secreted into tubules in normal kidney
. Secretion inc. when serum creatinine rises as w/ dec. in GFR
. Often overestimates the true GFR in patients w/ chronic renal disease
GFR in stages in kidney disease
1: kidney damage + normal/elevated GFR (over 90 mL)
2: kidney damage+mild GFR dec. (60-89 mL)
3: moderate dec in GFR (30-59)
4: severe dec. in GFR (15-29)
5: failure (under 15 or on dialysis)
T/F GFR dec. w/ age
T
eGFR equations
. Prediction equation
. Cockcroft-Gault formula: (140-age)(body wt kg)/(72)(serum creatinine) and multiple by 0.85 for women
. CDK-EPI and MDRD study equations: MDRD for GFR under 60 ml, CDK-EPI for over 60 ml
. Both equations use serum creatinine, age, sex, and ethnicity
. Issues when age/body size is extreme, malnutrition or obesity occurs, skeletal m. Disease, paraplegia, vegetarian diet, rapidly changing kidney function, or pregnancy
Relationship btw plasma creatinine and GFR
.. if GFR dec. and creatinine production is constant, then plasma creatinine inc.
. Inverse relationship
. Only good over time
. Mild renal insufficiency may not have serum creatinine inc. much so it is considered insensitive index
. This is due to kidney inc. secretion of creatinine when serum creatinine begins to rise
. Large dec. in GFR before plasma creatinine exceeds the upper range of normal
Clearance of para-aminohippuric acid (PAH)
. Estimate of renal plasma flow (RPF)
. PAH cleared from blood in 1 pass through kidney
. Tubule has large capacity to secrete PAH
. Excretion of PAH in urine = entry via RPF
. Clearance of PAF (ml/min) from kidney is estimate of RPF
How PAH is removed
. Removed from plasma by filtration and by secretion into prox. Tubule
. As long as secretory mechanism isn’t overwhelmed nearly all PAH entering kidney is excreted
Filtration fraction
. GFR/RPF
. Normally 0.15-0.2
. Higher the fraction, the greater the fraction of plasma that is filtered, the more solute available for excretion
. Can change since GFR and RPF are independent of one another
how to tell if freely filtered substance is secreted or reabsorbed
. Clearance over GFR: must also be. Secreted
. Clearance under GFR: must also be reabsorbed
. Substance cannot have clearance greater than renal plasma flow
Protein-bound solutes
. Not available for filtration
. Endogenous compounds (steroids, thyroid hormone, exogenous compounds, drugs)
. If it is 100% protein bound then none of the solute will be filtered
. If solute only partially protein bound, then only the fraction of the solute that is free in the plasma is available for filtration
. Drug that is protein bound it will have longer half-life
