Term
| what are the various categories of transport? |
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Definition
| passive diffusion (non coupled), filtration (solvent drag), facilitated passive diffusion, primary active transport, and secondary active transport-co-transport |
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Term
| what defines passive or non-coupled diffusion? |
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Definition
| high->low conc, no interaction between the material and the membrane - example being the aquaporin system in lipid membranes |
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Term
| what is filtration/solvent drag? what is an example of this at work? |
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Definition
| filtration is the movement of water across a semipermeable membrane in response to net hydrostatic/oncotic gradients (created by Na+ active transport). solvent drag is the transport of an osmotically active molecule (Mg, etc) across a water permeable membrane - the filtration of the water "drags" the dissolved solute along. for ex - on the brush border/apical cells, Na+ channels allow diffusion of Na+ passively into the negative cells. in between the cells (the squeezed shut component of the semipermeable membrane), the Na+ is then actively transported out, increasing the osmolarity, causing water to move into that pericellular space -> and eventually the water moves into the interstitum *carrying with it Mg and other ions (the solutes which are "dragged") |
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Term
| are carrier based transport systems saturable? |
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Definition
| yes, as the solute concentration on one side of the membrane increases - the ability of that solute to be transported increases to a point and then plateaus (or becomes saturated) when all the carrier proteins are engaged |
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Term
| what defines facilitated passive diffusion? |
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Definition
| it uses a carrier molecule which solute binds to and is then transported across the membrane along its concentration gradient. is saturable and generally faster than diffusion w/out carrier molecules |
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Term
| what is primary active transport? |
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Definition
| movement of solute across an electrochemical gradient, via energy provided by ATP (like the Na/K pump, where Na moves against the gradient and K moves with it) |
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Term
| what is the co-transport mechanism? |
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Definition
| this involves the movement of 2+ molecules and a carrier protein. one molecule moves along its concentration gradient, providing the energy for the other molecule moving against its concentration gradient. one example would be the Na+/glucose co-transport mechanism where Na+ moves along its gradient into the cell, bringing with it glucose, which is going against it's gradient using the energy generated by the Na= molecule |
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Term
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Definition
| carrier proteins that carry a single solute species |
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Term
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Definition
| carrier molecules that carry 2 or more solute species in the same direction |
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Term
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Definition
| carrier molecules that carry 2 or more solute species in different directions |
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Term
| what does excretion equal when referring to reabsorption and secretion? |
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Definition
| in reabsorption: excretion = filtered load - reabsorption. in secretion: excretion = filtered load + secretion. |
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Term
| what is the level of plasma glucose after which glucose starts to become excreted (threshold transport maximum)? |
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Definition
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Term
| what is the highest rate that glucose can be filtered out of the blood by the kidneys (renal transport maximum)? |
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Definition
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Term
| what comes first, the threshold transport maximum or the renal transport maximum? |
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Definition
| the threshold transport maximum |
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Term
| what are some things that would change the renal transport maximum? |
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Definition
| the relative rate of Na+ reabsorption, the total number of nephrons which are available, the total number of carriers available or, indirectly, the amount of energy available for secondary active transport. for example, if the GFR is increased, more fluid is transported into the proximal tubules per unit time - which is thought to balloon-out the PCT and uncover more transport sites |
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Term
| how much glucose should the kidney reabsorb? |
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Definition
| 100% - glucose is not supposed to be regulated by the kidney (the normal filtered load of glucose is 130 mg/min, while the max transport rate is 375 - way higher) |
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Term
| what is the normal plasma conc of glucose? |
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Definition
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Term
| where is most filtered glucose reabsorbed? |
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Definition
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Term
| what determines the fact that phosphate levels are regulated by the kidney (as opposed to glucose)? where is it mainly reabsorbed? |
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Definition
| the maximal transport rate of phosphate is 100 uM/min while the filtered load is 130 uM/min - meaning that more phosphate is being filtered than the tubules can maximally reabsorb per unit time - therefore there will always be phosphate excreted into the urine under normal conditions. phosphate is mainly reabsorbed in the PCT |
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Term
| what are factors that can decrease the rate of phosphate reabsorption? |
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Definition
| increased PTH, increased ACTCH (decreases the max rate of phosphate reabsorption), and a decreased rate of Na+ reabsorption |
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Term
| what are factors that can increase the rate of phosphate reabsorption? |
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Definition
| increased vit D3 and increased plasma Ca++ |
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Term
| do the kidneys play a role in regulation of sulfate? |
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Definition
| yes, the plasma concentration is 1.2 mM/L and the maximal transport rate is low at .06 mM/min - suggesting that the kidneys play a significant role in controlling the concentration of circulating sulfate |
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Term
| where in the nephron is sulfate reabsorbed? |
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Definition
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Term
| are there any factors which can affect the reabsorption of sulfate? |
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Definition
| there is competition between reabsorption of sulfate and glucose - the more glucose reabsorbed, the less sulfate reabsorbed |
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Term
| are amino acids regulated by the kidney? |
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Definition
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Term
| what area of the nephron is responsible for reabsorption of amino acids? |
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Definition
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Term
| what is the normal plasma concentration of amino acids in the blood? |
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Definition
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Term
| are there separate transporters for neutral, basic, and acidic amino acids? |
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Definition
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Term
| what factors can affect amino acid reabsorption? |
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Definition
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Term
| what are other materials handled by active transporters in the kidneys? |
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Definition
| organic anions/cations, uric acid, and proteins |
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Term
| what is a method of ensuring medications can stay in the body longer? |
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Definition
| to saturate the carrier proteins it uses in the kidneys |
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Term
| what are some measures of renal function? |
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Definition
| total renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction (FF), and filtered load (FL) |
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Term
| what is normal total RBF? |
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Definition
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Term
| how is renal plasma flow (RPF) calculated? |
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Definition
| the renal blood flow x(1-hematocrit) or RPF = (1200 mL/min)x(1-45%) = 660 mL/min |
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Term
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Definition
| the measure of filtration of renal plasma flow of all glomeruli, usually 130 ml/min |
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Term
| what is the filtration fraction (FF)? |
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Definition
| the GFR/RPF (130 ml/min / 660 ml/min = .2) this means that ~20% of the blood entering the kidneys enters the nephron. |
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Term
| how do kidney filtrate and plasma compare? |
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Definition
| they are identical, but the filtrate simply lacks cells and large plasma proteins |
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Term
| what is the filtered load? |
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Definition
| the amount of substance that is filtered per unit time. for *freely filtered substances: FL = GFR x [plasma conc of substance] |
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Term
| is GFR a crucial determinant of renal function? are there many variables that affect it? |
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Definition
| yes, GFR is a crucial determinant of renal function and its regulation is straightforward physically - but functionally complex b/c of the high number of regulated variables |
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Term
| what are the main things that determine the filtration rate of glomerular capillaries? |
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Definition
| hydraulic permeability, their surface area, and the net filtration pressure which is usually about 10 mm Hg. (NFP = Pgc – Pbc – πgc + πbc). Kf is a coefficient that combines hydraulic permeability and the glomerular surface area and is reffered to as the "filtration coefficient" NFP is starling's equation (NFP = PGC – PBC – πGC + πBC ) |
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Term
| what is starling's equation as it applies to the ? |
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Definition
| NFP = Kf(Pgc – Pbc) – Kp(πgc + πbc). where Pgc is the glomerular hydrostatic pressure (higher than systemic capillaries, usually ~60), Pbc is the bowman's capsule hydrostatic pressure (higher than interstitial fluid), πgc is the glomerular colloid osmotic pressure, and πbc is the bowman's capsule colloid osmotic pressure (should be 0 as proteins should not be filtered through the glomerulus). Kp is the reflection (rejection) coefficient for proteins (should be constant for each particular molecule, for ex, glucose and water have a filterability of 1, meaning they can filter - but most proteins have a very low filterability, usually < .70) |
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Term
| what are the anatomical factors affecting GFR? |
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Definition
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Term
| what are the physiological factors affecting GFR? |
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Definition
| hydrostatic and intersitial tissue changes |
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Term
| what are the 3 levels of filtration of the glomerular filtration barrier? |
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Definition
| 1) the endothelial cells, 2) basement membrane (lamina rara interna, lamina densa, and larmina rara externa), 3) the foot processes of the podocytes (these form filtration slits) |
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Term
| what are 2 factors that can affect the movement of solute across the semipermeable barrier of the glomerulus? |
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Definition
| size/steric factors and electrostatic factors |
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Term
| what does a filterability of 1 mean? what do most proteins have? |
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Definition
| the molecule has the same glomerular filterability as water - which is a constant based on size. most proteins have a filterability of <.75 - meaning they filter <75% as well as water |
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Term
| for a given size or filterability, how does a negative, neutral or positive charge on a molecule affect its ability to filter? |
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Definition
| neutral and positive charged molecules filter more freely than those negatively charged |
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Term
| how does decreased Kf (glomerular surface area) affect GFR? |
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Definition
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Term
| how does increased renal arterial pressure affect GFR? RBF? |
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Definition
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Term
| how does increased afferent arteriolar constriction affect the GFR? RBF? |
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Definition
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Term
| how does increased efferent arteriolar resistance affect GFR? RBF? |
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Definition
| it increases GFR and decreases RBF |
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Term
| how does increased afferent and efferent arteriolar dilation affect GFR and RBF? |
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Definition
| GFR is unaffected due to countering forces, but RBF will go down |
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Term
| how would an increase in intratubular pressure affect GFR? |
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Definition
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Term
| how would an increase in systemic plasma oncotic pressure affect the GFR? |
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Definition
| it would decrease the GFR (this would pull water back from leaving the glomerulus) |
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Term
| how would decrease in plasma renal flow affect the GFR? |
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Definition
| it would decrease the GFR |
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Term
| what does intrinsic control of renal blood flow accomplish? |
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Definition
| this allows renal blood flow and thus GFR to remain at a constant rate between fluctuations in arterial pressure. cells in the walls of the arterioles are sensitive to these changes and adjust the vasoconstriction/dilation accordingly |
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Term
| what is the main purpose of the juxtaglomerular apparatus in the DCT? |
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Definition
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Term
| how does the juxtaglomerular apparatus in the DCT maintain the GFR? |
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Definition
| macula densa cells in the juxtaglomerular apparatus sense the workload of efferent arterioles via absorption of Na+ taking place (indicative of GFR) and can thus adjust the GFR via the RAA axis and constriction of efferent arterioles (increases GFR) |
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Term
| wikipedia description of macula densa function: |
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Definition
A decrease in blood pressure causes a decrease in the GFR (glomerular filtration rate) which causes more reabsorption, resulting in a decreased concentration of sodium and chloride ions at the macula densa and triggers an autoregulatory response to increase reabsorption of ions and water in order to return blood pressure to normal. Reduced blood pressure means decreased venous pressure and hence a decreased peritubular capillary pressure. This causes a smaller capillary hydrostatic pressure which causes an increased absorption of sodium ions into the vasa recta at the proximal tubule. Because of this increased absorption, less NaCl is present at the distal tubule which is where the macula densa is located. The macula densa senses this drop in salt concentration and responds through two mechanisms: first, it triggers dilation of the renal afferent arteriole, decreasing afferent arteriole resistance and thus offsetting the decrease in glomerular hydrostatic pressure caused by the drop in blood pressure. Second, macula densa cells release prostaglandins, which triggers granular juxtaglomerular cells lining the afferent arterioles to release renin into the bloodstream. (The juxtaglomerular cells can also release renin independently of the macula densa, as they are also triggered by baroreceptors lining the arterioles, and release renin if a fall in blood pressure in the arterioles is detected.) Furthermore, activation of the sympathetic nervous system stimulates renin release through activation of beta-1 receptors.
The process triggered by the Macula densa helps keep the glomerular filtration rate (GFR) fairly steady in response to varying artery pressure, due to dilation of the afferent arterioles and the action of Renin, which triggers constriction of the efferent arterioles, both of which increase hydrostatic pressure in the glomerulus. |
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Term
| what is the net result of the macula densa cells sensing decreased NaCl in the DCT (due to increased reabsorption due to decreased arterial pressure - which causes ultimately decreased peritubular hydrostatic pressure and resultant increased NaCl uptake *OR increased PCT NaCl uptake)? |
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Definition
| the macula densa directly decreases the afferent arteriolar resistance (dilation) and via the RAA axis increases the efferent arteriolar resistance (constriction) |
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Term
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Definition
| the rate at which the kidneys clear various substances from the plasma, which provides an effective measure of the functional state of the kidneys (it is always expressed in units of volume per time) |
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Term
| how is clearance of a certain substance calculated? |
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Definition
| the urine conc of that substance times the urine flow (per min) divided by the plasma concentration of that substance. Cs = Us x V / Ps |
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Term
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Definition
| the rate at which the kidneys clear various substances from the plasma, which provides an effective measure of the functional state of the kidneys (it is always expressed in units of volume per time) |
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Term
| how is clearance of a certain substance calculated? |
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Definition
| the urine conc of that substance times the urine flow (per min) divided by the plasma concentration of that substance. Cs (mL/min) = Us (mg/mL) x V (mL/min) / Ps (mg/mL) (note that the unit for clearance is volume per unit time and NOT amount (mg) of substance S per time) |
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Term
| what is a substance that can be used to determine GFR? why? |
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Definition
| inulin is freely filtered across the glomerulus, but is neither reabsorbed by the nephron nor secreted - the only way what inulin can reach the urine is by crossing the glomerular filtration barrier, and therefore inulin's clearance can be used to calculate GFR (Cs = GFR of inulin) |
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Term
| how is inulin used to calculate GFR? |
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Definition
| the Cs of inulin is equal to its GFR, so: GFR = (inulin urine conc x inulin urine flow)/)inulin plasma conc. so if total urine conc of inulin = 37,500 mg/300mL = 125 mg/mL and if 300 mL is collected in 5 hrs, urine flow= 1 mL/min and if plasma conc of inuline is 1 mg/mL, then (125x1)/1 = 125, and the kidney tested's inulin Cs is 125 ml/min which is also the kidneys GFR due to inulin's properties. |
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Term
| why is creatinine used as an indicator of GFR? |
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Definition
| there is a negligible amount of creatinine secreted in the nephron, however for the most part the kidney excretes all the creatinine in the blood except for a constant 1 mg/dL plasma level. if this plasma level is higher than 1 mg/dL, then can be assumed that the glomeruli are filtering at a lower rate than normal |
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Term
| is there a direct relationship between a rise in plasma creatinine and a reduction in GFR? |
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Definition
| yes there is a direct inverse relationship, where if plasma creatinine levels are 2 mg/dL (2x normal level), then the GFR can be safely assumed to have been reduced by 50% (if GFR is reduced by 1/2, plasma conc of creatinine does not rise indefinitely - it stabilizes at 2 mg/dL) |
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Term
| why is para amino hippuric acid (PAH) used to determine renal plasma flow? |
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Definition
| PAH is about 90% completely cleared from the kidney (no known substance is 100% cleared), in that it is freely filtered, not reabsorbed, not metabolized and is *almost completely secreted into the tubular fluid by the tubules (remember only 20% of total plasma flow is subject to GFR in the glomerulus) |
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Term
| how is para amino hippuric acid (PAH) used to determine renal plasma flow? |
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Definition
| (Upah (urine PAH conc) x V (urine flow rate))/(Ppah PAH plasma conc) so if Upah = 5.85, V = 1 mL/min, and plasma conc of PAH is .01 then total PAH clearance = 585 mL/min. to adjust for the physiologic 90% complete clearance of PAH, divide 585 / .9 to get total renal plasma flow, which = 650 mL/min |
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Term
| how can total renal blood flow be determined using the total renal plasma flow? |
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Definition
| total renal blood flow = total renal plasma flow/(1-hematocrit), so total RBF = 650 mL/min /(1-.45) or 1182 mL/min |
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