Exam 9 - Urine Concentration & Osmolarity Control Flashcards
Osmolarity determined by
- total solute
- volume of ECF
Body water determined by
- fluid intake
- renal excretion of H2O…GFR and reabsorption
If ECF [solute] increases…
- Kidneys hold onto more H2O
- ECF solutes are diluted
- Opposite is also true
Water / solute changes to maintain homeostasis
- solute excretion same each day
- solue [ ] in ECF stays same
- changes in water excretion adjusted to keep ECF constant
Posterior pituitary and ECF osmolarity
- ECF osmolarity increases…. PP releases more ADH
- more ADH….more water reabsorption in distal and collecting
Urine volume and [ ]
- more water uptake…less urine volume…
- NORMAL amount of solute now in less water…
- produce small amount of very concentrated urine
- opposite also true
Max urine [ ]
- 500 mls/day
- 1200-1400 mOsm/L
Min urine [ ]
- 20 L/day
- 50 mOsm/L
- Low [ADH]
- drop water reabsorption from 124 to 111 mls/min
Normal GFR
125 mls/min
Normal urine output
1 ml/min
Drink 1 L of water
- decrease in ADH release
- changes in 45 min
- slight increase in solute excretion…due to drop in bulk flow/leak back
- slight decrease in plasma osmolarity…due to ingestion of H2O
- large decrease in urine osmolarity…600-100
- large increase in urine output…1-6
Filtrate Osmolarity = ?
Plasma osmolarity
300 mOsm/L
Main mechanism to get dilute urine
- decrease water reabsorption…no change in solute reabsorption
- increase in ADH
How to increase solute reabsorption
- increase angiotensin/aldosterone
Dilute urine… proximal tubule
- solute and water reabsorbed at same rate
- no change in osmolarity
- 300
Dilute urine…descending loop
- water absorbed following osmotic gradient
- urine [ ] increases 2-4x
- 300 to 600
Dilute urine…ascending loop
- Na/K/Cl reabsorption
- No water reabsorption
- tubular osmolarity drops to 100 by early distal
Dilute urine…distal and collecting
- variable amount of water reabsorbed…depending on ADH
- Normal solute reabsorption
- can drop to min of 50 mOsm/L
Obligatory urine volume
- minimum urine needed to excrete waste products
- normal 70kg person needs to excrete 600 mOsm/day
- 1200 mOsm/L…max renal osmolarity…max we can get rid of
- less in renal disease
- So…..0.5L/day is minimum urine we can excrete
If drinking 1L of 3.5% sea water
- get rid of normal 600 mOsm PLUS 1200 from sea water
- need to remove 1800mOsm…max is 1200 mOsm/L
- 1.5 liters need to be removed a day
- So….losing 500 mls day…get dehydrated
What is needed for high [ ] urine
- high ADH
- high osmolarity in renal interstitial fluid
- drives reabsorption too
- set up by countercurrent mechanism
Vasa recta and [ ] urine
- removes water as it is reabsorbed so that we keep osmolarity gradient which drives water out of tubule into body
Countercurrent mechanism and anatomy
- Long loops of henle in juxtameduallry nephrons (25%)
- vasa recta help pull away water…parallel to loops
- collecting ducts…parallel to loops also
Urine osmolarity and IF osmolarity
- urine [ ] cant exceed IF…gradient is what drives movement
- normal at bottom of loop is 600
- to get to 1200 (max)…need to move more solute into medulla
Hyperosmotic renal medulla
- made by accumulating solute
- maintained by inflow/outflow of water and solutes
- out of loop and collecting tubules/ducts
- into vasa recta…carry water and solute away to maintain gradient
Factors creating hyperosmotic medulla
- Na/K/2Cl transporter out of thick ascending
- can get 200 gradient
- active transport of ions from duct to medulla
- facilitated diffusion of urea from ducts to IF
- more solute absorbed in medullary IF than water
Process of concentrating urine
1 - pump solute out of ascending…100 mOsm out
- urine now more dilute
2 - water diffuses out of descending…100 also
- urine now more [ ] on this side…matches IF
3 - [ ] urine disperses throughout loop…over all osmolarity increases
4 - pump solute out of aces ending again…get overall 200 gradient
5 - water diffuses out of descending again… matches IF again
6 - repeats until urine [ ] is 1200 at bottom of medulla
Initial [ ] of urine entering distal
- low…100
- no water reabsorption in ascending
Urea and medullary osmolarity
- 40-50% of total osmolarity
- excrete 50% of filtered load
Urea and proximal tubule
- 50% of filtered land reabsorbed
- [ ] goes up….more water reabsorbed
Urea and thin loop
- descending…[ ] up….water reabsorbed
- descending/ascending…[ ] up…secretion of urea into tubule
- via UT-A2
Urea and thick ascending/distal/tubule/duct
- urea not permeable
- [ ] up in duct as large amounts of water reabsorbed
Urea and medulla collecting duct
- urea permeability increases…more urea into IF
- via UT-A1 and UT-A3 (A3 activated by ADH)
- water still reabsorbed…[ ] of urea still high
- some urea back into thin loop via UT-A2
- called urea loop
How to feed medulla w/o washing away concentrated solute
- low medulla blood flow….5% of renal flow
- vasa recta act as exchangers
Vasa recta characteristics
- permeable to solute…except protein
- start at cortical-medullary boundary
- as they descend…water out into IF / solute in from IF
- as ascend… water into blood from IF / solute out into IF
- carry away only enough to maintain gradient…nothing more
Increase BF to vasa recta
- will wash out solute
- drop solute [ ] in renal medulla
Caused by: - vasodilators
- large BP increase (small is autoregulated)
Change in osmolarity in proximal
- 65% ions reabsorbed
- flow goes from 125 to 44
- normal osmolarity
Change in osmolarity in descending
- tubular osmolarity matches IF
- higher…more so for [ ] urine
- high water permeability / low ion
- flow is 25
Change in osmolarity in thin ascending
- no water permeability
- normal reabsorption of ions
- drop in osmolarity
- flow still 25…no change in water [ ]
Change in osmolarity in thick ascending
- no water permeability
- large ion absorption….active
- osmolarity drops more
- flow still 25
Change in osmolarity in early distal
- diluting segment
- no water out
- large amount of ions out
- flow still 25
Change in osmolarity in late distal / cortical collecting tubule
- osmolarity based on ADH
- low ADH…no water reabsorption…flow still 25
- high ADH…water in…flow drops to 8
Change in osmolarity in medullary collecting tubule
- depends on ADH
- high ADH… high water reabsorb…urea [ ] up…flow 0.2
- low ADH…urea slightly reabsorbed…flow down to 20 only
How kidneys can make high [ ] urine
- use urea
- contains little/no Na or Cl…even though NaCl make 50-60%
- dehydration / low Na intake…increase angiotensin II and aldosterone
- kidneys can control urea and NaCl separately
How kidneys can make lots of urine w/o Na excretion
- change ADH…only affects H2O
Obligatory urine volume dictated by…
Max ability to [ ] urine….normal is 1200
- if kidney function drops….so does ability to [ ] urine
Normal Na
142 mEq/L
Normal Osmolarity
- 300 mOsm/L
- 291-309 is range…+/- 2 to 3%
Control over Na [ ] and osmolarity
- very precise
- important for distribution of H2O between compartments
Na and associated ions
94% of extracellular solute
- glucose and urea….3-5%
- Na not very permeable…large driving force
Plasma osmolarity equation
- 1 x [plasma Na]
2. 1 x 142 = 298 mOsm/L
2 systems that control ECF osmolarity and [Na]
- osmoreceptors - ADH system
- thirst mechanism
Osmoreceptor cells
- in anterior hypothalamus
- shrink if high ECF…send impulses to PP
- PP release ADH
Increase in osmolarity….
- increase water permeability in distal tubules/ducts
- more water reabsorbed…Na excreted at normal
Drop in BP/ volume
- increase in ADH
- barroreceptors / reflex pathway
ADH response to volume / osmotic changes
- small change in osmolarity (1%) trigger ADH release
- but low ceiling
- CBV must drop 10% to see ADH change
- but 15-20% drop in CBV has HUGE change in ADH
- not much ceiling
Hypoxia
- increase ADH
Morphine / Nicotine / cyclophosphamide
Increase ADH
Alcohol / Clonidine / Haloperidol
Drop ADH
Thirst mechanism
- control fluid intake…fluid loss in sweating, breathing, GI
- thirst center in brain…organum vasculosum
- stimulates ADH release if thirsty
- shuts off before we reach target value…prevent over-hydration
- don’t want to get into roller coaster situation
- stimulated with Na [ ] just 2 mEq above normal
Increase in angiotensin II / dryness of mouth
Increase thirst
Drop in angiotensin II / gastric distension
Drop in thirst
- angio II acts on organum vasculosum
How we maintain tight control over Na
- with thirst control AND osmoreceptor-ADH systems
- prevent large changes in Na even if Na intake is 6x normal
- only when both fail do we see change in Na [ ]
Angiotensin II and aldosterone role
- Na reabsorption
- NOT Na [ ]….water moves with Na so [ ] stays same….
- just overall AMOUNT changes with angio/ald
- high levels of ald will only move [ ] 3-5 mEq - increase in both will increase Na and water uptake
- LOSS of ald system can drop Na [ ]
