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29 Cards in this Set
- Front
- Back
Na+ transports in various segments
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- Each transports Na+ in different way
- Depends on 1) types of transporters present 2) Permeability of junctions between cells - Na+K+ATPase on basolateral side = common to all segments! - maintains low intracellular [Na+] using energy |
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Proximal tubule function
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- Main transporters = Glucose/Na+ cotransporter and H+/Na+ antiporter
- Na+/K+ ATPase = maintains low intracellular Na+ - Pumps Na+ into interstitial space - Keeps [Na+] in cell low - Na+ can flow from tubule lumen into cell WITH concentration gradient - Na+ leak through leaky tight junctions from lumen into interstitial space - [Na+] is pretty high in tubule -> high osmotic pressure makes it easy to get through leaky junctions - Na+ linked transporters for amino acids, PO4, SO4, lactate Thick ascending limb function;- Main transporters = Na+/K+/2Cl- cotransporter and Na+/H+ antiporter - Na+/K+/2Cl- cotransporter = site of action for diuretics - Lasix, other loop diuretics etc. -> blocks Na+/H2O reuptake via this cotransporter - K+ actually can enter back in on either side - Paracellular diffusion - minimal compared to proximal tubule - Much tigher junctions - No water reabsorbtion - helps keep urine dilute a little - Na+/K+ ATPase = maintains low intracellular Na+ |
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Distal convoluted tubule function
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- Have Na+/Cl- cotransporters
- No H2O reabsorption -> retain water, dilute urine - No paracellular transport - tight junctions, high resistance epithelium - Na+/K+ ATPase = maintains low intracellular Na+ |
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Collecting duct function
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- No cotransports - epithelial Na+ channel (ENaC)
- ENaC = primary site of action for hormonal water/electrolyte balance - Channels open more/less to reabsorb water or not - Based on hormonal fine tuning - K+ channels also - K+ secretion here is key for K+ homeostasis - Na+/K+ ATPase = maintains low intracellular Na+ - No paracellular transport |
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Micropuncture analysis to evaluate tubular function
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- Basically important way of sampling tubule fluid
- Shows how tubule modifies the filtrate - Access limited to superficial segments (not loop of Henle, etc.) |
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Micropuncture study shows [inulin, others] changes over the length of proximal tubule
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- Compares [inulin, others] in tubule/[inulin] in plasma
- Inulin can't be secreted or reabsorbed - Thus, if inulin concentration rises -> water is being reabsorbed - If [tubule]/[plasma] = 2, then 50% of water has been reabsorbed! - Key point - Na+ line is horizontal = 1.0 ratio - Means that Na+ is reabsorbed at same rate as water - Remains iso-osmotic! |
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Uptake of reabsorbed fluid into peritubular capillaries & Starling forces
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- Reabsorption = Kf(Net forces)
- Pc = hydrostatic peritubular capillaries - Pif = hydrostatic interstitium - πc = colloid pressure of peritubular capillaries - πif = colloid interstitial space |
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Starling force trend overview
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- Glomerular capillary - favors filtration
- High PG, moderate πG - Peritubular capillary = favors reabsorption - Low Pc, High πc - Alteration of blood flow -> can increase Pc -> less reabsorbtion - Results in net loss of Na+ and H2O |
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Glucose reabsorption
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- Occurs almost exclusively at proximal tubule
- SGLT1 = Na+/glucose co-transporter - based on gradient from ATPase! - GLUT1 and GLUT2 = glucose enters interstitial space via these - Na+ independent diffusion |
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Glucose reabsorption limits
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- As filtered load increases - threshold at which 100% reabsorption not possible
- Begin to see excretion - Often see glucose in urine of diabetics - past the threshold - Transporters get saturated |
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2 ways to increase filtered load of glucose
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- Increase hydrostatic pressure -> increased GFR
- Increase the [glucose] in plasma |
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Amino acid/peptide reabsorption
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- AA reabsorbed via Na+/AA cotransporters using Na+ gradient
- Mostly in proximal tubule - Proteases at brush borders - often break down proteins - AA taken up by co-transporter -> back to circulation |
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Reabsorption of albumin
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- Receptor mediated endocytosis!
- Albuminuria = Albumin in urine - assumed to be glomerular effect...might not always be - Probably some increased glomerular permeability, but might also be related to endocytotic method! |
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Body fluid dynamics
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- Intake has to match the output - otherwise will be out of balance
- Intake, sweat, urine all contribute |
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Obligatory urine volume
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- Minimum amount of water that is lost to keep tissue osmolality in balance
- Produce waste via metabolism - need to get rid of it - Thus, need some water to excrete it |
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Minimum excretion and Maximum concentrating ability
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- Must excrete 600 mOsmoles/day to live
- Max concentrating ability -> ~1200 mOsm/L - Thus, with minimum excretion and max concentration: = 600/1200 = 0.5 liters per day MINIMUM! - Generating hyperosmotic urine saves water! - Plasma is ~300 mOsm/L - Iso-osmotic to urine = ~2L of urine/day! |
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Maximum urine excretion and minimum concentration
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- Minimum concentration = ~30 osm/L
- Still need to get rid of 600 mOsmoles/day of waste - Thus 600/30 = 20 liters of urine! - This is the max volume without losing excess ions - More volume -> matching output -> loss of ions -> "dilutional hyponatremia" |
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Free water clearance
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- Plasma has ideal [] of ~300 mOsm/L - water present above this level = Free water!
- Essentially the clearance of water above and beyond what's necessary for normal plasma content |
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Calculating free water clearance
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- Clearance of osmolites same as before
= Cosm = (Uosm * V)/Posm - Urine flow has two components = V = Cosm + H2Oosm - Thus, CH2O = V - Cosm *** Negative values = retaining free water! - Most of the time we have negative clearance! |
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Free water clearance trend
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- CH2O is really related to the relationship of Uosm to Posm
- CH2O = 0 when Uosm = Posm - CH2O > 0 when Uosm < Posm - CH2O < 0 when Uosm > Posm |
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Graph of osmolality in different segments of nephron
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- Graph with tubular fluid (TF)/plasma osmolality
- At proximal tubule TF/P = 1.0 - Reabsorption at tuble = iso-osmotic - Dehydrated state - peaks at loop of Henle, decreases - increases again at collecting duct - Concentration of excreted product ~ concentration in loop of Henle - High water intake = very small peak at loop of Henle - Concentration continues to fall until excreted |
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Water reabsorption in collecting duct
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- Duct runs back from cortex towards inner medulla
- From iso-osmotic (~300 mOsm) at cortex to hyperosmotic - Favors resorption of water as it flows down collecting duct! *** BUT collecting duct may/may not be permeable to water based on conditions! |
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Strategy for making dilute urine
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- Collecting duct is impermeable to water, but Na+ continues to be reabsorbed by transporters
- Water can't be reabsorbed even with the gradient - Overall = continue Na+, Cl- reabsorption while inhibiting water movement |
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Strategy for making concentrated urine
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- Collecting duct IS permeable to water
- Water flows out as osmotic pressure increases along duct - End product is much more concentrated *** Limit of concentration = ~medullary interstitium |
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3 essential factors of osmotic gradient in medulla
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1) Counter current multiplier of Na+ and Cl-
- Set up by unique anatomical arrangement of Loop of Henle 2) Reabsorption of urea, and recycling/trapping it in vasa recta 3) Counter current exchanger in vasa recta capillaries - Helps preserve gradient without washing it out |
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Counter current multiplier
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- Relies on fact that segments transport Na+ and H2O differently
- Thick ascending limb = active Na+, impermeable to water - Thin descending limb = impermeable to Na+, permeable to water - Putting these together - get multiplication effect! |
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4 steps of counter current multiplication
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1) Active transport of Na out of Thick ascending limb to interstitial space
2) Passive water moves out of thin descending limb to eq. [Na] in the interstitium 3) Flow - entering fluid continually gives up H2O to eq. -> progressively becomes more concentrated 4) New fluid continually brings new solute - repeated over and over again *** NaCl Gets you to about 600 mOsm/L - other 600 from urea! |
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Urea recycling
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- From collecting duct to vasa recta
- Urea transporters active during dehydrated states - Comes back out, eq. with the interstitium - Generates other 600 mOsm/L - Reabsorbed into vasa recta |
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Counter current exchanger in vasa recta
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- Key for maintaining osmotic gradient - Entirely passive system!
- Descending vasa recta - loses H2O, gains solute - Ascending vasa recta - gains H2O, loses solute - Slow flow preserves osmotic gradient as vasa recta loop continuously tries to eq. with surrounding interstitium - Fast flow - can wash out solute! - Thus - increased BP or flow = loss of Na+, etc. |