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29 Cards in this Set

  • Front
  • Back
Na+ transports in various segments
- 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
Proximal tubule function
- 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+
Distal convoluted tubule function
- 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+
Collecting duct function
- 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
Micropuncture analysis to evaluate tubular function
- Basically important way of sampling tubule fluid
- Shows how tubule modifies the filtrate
- Access limited to superficial segments (not loop of Henle, etc.)
Micropuncture study shows [inulin, others] changes over the length of proximal tubule
- 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!
Uptake of reabsorbed fluid into peritubular capillaries & Starling forces
- Reabsorption = Kf(Net forces)
- Pc = hydrostatic peritubular capillaries
- Pif = hydrostatic interstitium
- πc = colloid pressure of peritubular capillaries
- πif = colloid interstitial space
Starling force trend overview
- 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
Glucose reabsorption
- 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
Glucose reabsorption limits
- 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
2 ways to increase filtered load of glucose
- Increase hydrostatic pressure -> increased GFR
- Increase the [glucose] in plasma
Amino acid/peptide reabsorption
- 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
Reabsorption of albumin
- 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!
Body fluid dynamics
- Intake has to match the output - otherwise will be out of balance
- Intake, sweat, urine all contribute
Obligatory urine volume
- 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
Minimum excretion and Maximum concentrating ability
- 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!
Maximum urine excretion and minimum concentration
- 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"
Free water clearance
- 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
Calculating free water clearance
- 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!
Free water clearance trend
- 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
Graph of osmolality in different segments of nephron
- 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
Water reabsorption in collecting duct
- 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!
Strategy for making dilute urine
- 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
Strategy for making concentrated urine
- 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
3 essential factors of osmotic gradient in medulla
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
Counter current multiplier
- 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!
4 steps of counter current multiplication
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!
Urea recycling
- 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
Counter current exchanger in vasa recta
- 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.